Serum Intestinal Fatty Acid Binding Protein Research Articles

Low abdominal near-infrared spectroscopy values and elevated serum intestinal fatty acid-binding protein predict necrotizing enterocolitis in a premature piglet model

METHODS: Human neuroblastoma cells (KELLY) were injected into the left adrenal gland of Nude mice to create an orthotopic xenograft. When tumor volume reached 300mm3 (measured by ultrasound) 60-80% of the tumor was resected with electrocautery. A 7x11mm doxorubicin(200mg)-loaded sustained released silk film (DOX-film) was applied to the residual tumor cavity for six animals; silk films without doxorubicin (CONT-film) were applied in five animals. Subsequent tumor volume was followed for 28 days; tumor histology was analyzed with H&E, TUNEL assay, and Ki67. In vitro release profile of DOX-film was also measured. A repeated-measures generalized linear model was conducted with tumor volume as the outcome, DOX-film group and post-resection days as main effects, and a group-time interaction term.

242 Evaluation of the size and contraction of the gallbladder by ultrasound in cystic fibrosis patients with and without pancreatic insufficiency

Objectives: Previous studies suggest a cystic fibrosis (CF) enteropathy. It can be hypothesized that this enteropathy contributes to the characterizing poor nutritional status, gradual decline in pulmonary function and subsequent mortality in these patients. This study aimed to investigate enterocyte damage and intestinal inflammation in CF, and its relation to pulmonary function. Methods: Serum intestinal fatty acid binding protein (I-FABP), a circulating marker for enterocyte damage, was analysed in a cohort of 72 CF patients and 107 controls. Data regarding faecal calprotectin − a marker for intestinal inflammation, pulmonary function, and comorbidities were extracted from the medical charts. Conclusion: I-FABP levels were significantly elevated in CF patients as compared to controls (502 pg/ml [281–774] and 288 pg/ml [147–349], p< 0.001). Serum I-FABP was negatively correlated with forced expiratory volume (FEV1) in children (rp −0.589, p< 0.05, n = 15). Calprotectin levels were elevated in 93% of CF patients, and correlated positively with age (rs 0.350, p< 0.05, n = 20) and negatively with FEV1 in adults (rs −0.440, p< 0.01), even after correction for age. Patients with CF-related diabetes (CFRD), exocrine pancreatic insufficiency (EPI) and patients using protonpompinhibitors (PPIs), showed elevated calprotectin levels. In this study, for the first time, enterocyte damage in CF is demonstrated using I-FABP as a marker. Presence of intestinal inflammation in CF patients was confirmed and now shown to be worse in EPI, CFRD and PPI use. Moreover, the data of this study suggest a relation between intestinal damage and inflammation and pulmonary function.

Limb Remote Ischemic Preconditioning for Intestinal and Pulmonary Protection during Elective Open Infrarenal Abdominal Aortic Aneurysm Repair

Remote ischemic preconditioning (RIPC) may confer the cytoprotection in critical organs. The authors hypothesized that limb RIPC would reduce intestinal and pulmonary injury in patients undergoing open infrarenal abdominal aortic aneurysm repair. In this single-center, prospective, double-blinded, randomized, parallel-controlled trial, 62 patients undergoing elective open infrarenal abdominal aortic aneurysm repair were randomly assigned in a 1:1 ratio by computerized block randomization to receive limb RIPC or conventional abdominal aortic aneurysm repair (control). Three cycles of 5-min ischemia/5-min reperfusion induced by a blood pressure cuff placed on the left upper arm served as RIPC stimulus. The primary endpoint was arterial-alveolar oxygen tension ratio. The secondary endpoints mainly included the intestinal injury markers (serum intestinal fatty acid-binding protein, endotoxin levels, and diamine oxidase activity), the markers of oxidative stress and systemic inflammatory response, and the scores of the severity of intestinal and pulmonary injury. In limb RIPC group, a/A ratio was significantly higher than that in control group at 8, 12, and 24 h after cross-clamp release (66 ± 4 vs. 45 ± 4, P = 0.003; 60 ± 6 vs. 37 ± 4, P = 0.002; and 60 ± 5 vs. 47 ± 6, P = 0.039, respectively). All biomarkers reflecting intestinal injury increased over time, and there was significant differences between limb RIPC and control group (P < 0.001). The severity of intestinal and pulmonary injury was decreased by limb RIPC (P = 0.014 and P = 0.001, respectively). Limb RIPC attenuates intestinal and pulmonary injury in patients undergoing elective open infrarenal abdominal aortic aneurysm repair without any potential risk.

Serum I‐FABP as marker for enterocyte damage in coeliac disease and its relation to villous atrophy and circulating autoantibodies

Enterocyte damage is the hallmark of coeliac disease (CD) resulting in malabsorption. Little is known about the recovery of enterocyte damage and its clinical consequences. Serum intestinal fatty acid binding protein (I-FABP) is a sensitive marker to study enterocyte damage. To evaluate the severity of enterocyte damage in adult-onset CD and its course upon a gluten-free diet (GFD). Furthermore, the correlation among enterocyte damage, CD autoantibodies and histological abnormalities during the course of disease is studied. Serum I-FABP levels were determined in 96 biopsy-proven adult CD patients and in 69 patients repeatedly upon a GFD. A total of 141 individuals with normal antitissue transglutaminase antibody (IgA-tTG) levels served as controls. I-FABP levels were related to the degree of villous atrophy (Marsh grade) and IgA-tTG. I-FABP levels were elevated in untreated CD (median 691 pg/mL) compared with controls (median 178 pg/mL, P < 0.001) and correlated with Marsh grade (r = 0.265, P < 0.05) and IgA-tTG (r = 0.403, P < 0.01). Upon a GFD serum levels decreased significantly, however, not within the range observed in controls, despite the common observed normalisation of IgA-tTG levels and Marsh grade. CD patients with elevated I-FABP levels nonresponding to GFD showed persistent histological abnormalities. Enterocyte damage assessed by serum I-FABP correlates with the severity of villous atrophy in coeliac disease at the time of diagnosis. Although enterocyte damage improves upon treatment, substantial enterocyte damage persists despite absence of villous atrophy and low IgA-tTG levels in the majority of cases. Elevated I-FABP levels nonresponding to gluten-free diet are indicative of histological abnormalities and warrant further evaluation.

Additional value of serum I-FABP levels for evaluating celiac disease activity in children

Objectives. Addition of a non-invasive marker for intestinal damage to the currently used parameters for celiac disease activity (symptoms, serologic tests and biopsy) might further improve clinical management of celiac disease (CD). Intestinal fatty acid binding protein (I-FABP) is a cytosolic enterocyte protein and sensitive marker for enterocyte damage in the small intestine. We investigated whether serum I-FABP levels can reliably identify villous atrophy in children with a positive CD antibody screening. Moreover, the recovery of I-FABP levels after gluten free diet (GFD) was studied. Methods. I-FABP levels were analyzed retrospectively in 49 children with biopsy proven CD and in 19 patients with a positive screening but without histological confirmation of CD. Blood was collected before biopsy and repeatedly after the onset of GFD. Results. Initial I-FABP concentrations in CD (median 458 pg/ml) were significantly (p < 0.001) elevated compared to controls (median 20 pg/ml). In the control group, only two of 19 children were found to have elevated I-FABP levels, of which one was subsequently diagnosed with CD after gluten challenge. I-FABP concentrations correlated with severity of villous atrophy. In all CD patients, I-FABP levels decreased quickly after GFD and normalized in 80% of patients within 12 weeks. Conclusions. Elevated I-FABP levels accurately predict villous atrophy in children with a positive serologic test for CD (positive predictive value 98%). In addition, measurement of I-FABP enables monitoring the response to GFD.

Serum Intestinal Fatty Acid Binding Protein and Phosphate Levels in the Diagnosis of Acute Intestinal Ischemia: An Experimental Study in Rabbits

BackgroundAcute intestinal ischemia is a serious clinical disorder with mesenteric infarction, which has high mortality. It is important to establish a biochemical marker for the early diagnosis of acute intestinal ischemia. ObjectivesThe aim of this experimental study was to assess the changes in the serum levels of intestinal fatty acid binding protein (IFABP) and phosphate by time using the acute intestinal ischemia model in rabbits. MethodsIn this study, 21 New Zealand rabbits were randomly divided into three groups. Blood samples were obtained at 0, 1, 3, and 6 h in the control group. Blood samples were obtained at 0, 1, 3, and 6 h in the sham group after simple laparotomy. Blood samples were obtained at the same hours in the ischemia group after simple laparotomy and ligation of the superior mesenteric artery. ResultsThere was no significant difference between the control, the sham, and the ischemia groups in terms of serum IFABP levels at any time (p > 0.05). Serum phosphate levels significantly increased in the ischemia group (p < 0.001). Studies on IFABP have begun emerging in the literature, and there is no standard approach for the technique to measure the IFABP level. No studies on IFABP were found in the literature on rabbits. ConclusionBased on our results, the role that IFABP levels play in the diagnosis of acute intestinal ischemia is unclear at this time. Serum phosphate levels continued to rise as the duration of ischemia was prolonged. These findings support the suggestion that serum phosphate levels are valuable for the diagnosis of acute intestinal ischemia.

Serum intestinal fatty acid binding protein level for early diagnosis and prediction of severity of necrotizing enterocolitis

Background/Aim Intestinal fatty acid binding protein (I-FABP) is found within cells at the tip of the intestinal villi, an area commonly injured in necrotizing enterocolitis (NEC). In this study, we aimed to investigate the value of serum I-FABP in early diagnosis and predicting severity of NEC. Methods This prospective study was conducted between April 2009 and November 2009. The preterm infants with suspected NEC were included in the study. These infants were divided into two groups according to their final diagnoses; Group 1: Stage 1 NEC and Group 2: Stages 2–3 NEC (Group 2a: Stage 2 NEC, Group 2b: Stage 3 NEC). Healthy preterms were assigned to control group (Group 3). Serial blood samples were obtained from the patients at symptom onset, 24 h and 72 h later. One blood sample was taken from the controls. Serum I-FABP levels were compared among the groups. Results Initial serum I-FABP concentrations were 324.0 ± 165.8 pg/ml, 764.7 ± 465.1 pg/ml, and 360.2 ± 439.5 pg/ml in Group 1, Group 2a, and Group 2b, respectively, and all were significantly higher than those of the control group (76.9 ± 115.9 pg/ml) ( p < 0.001). The serum I-FABP levels gradually decreased from the onset of the disease to 72nd hour in Group 1 and Group 2a ( p = 0.001). In Group 2b I-FABP concentrations slightly decreased at 24th hour of the disease and increased thereafter, but the difference was not significant (p = 0.06). Conclusion Serial measurements of I-FABP levels may be a useful marker for early diagnosis and prediction of disease severity in NEC.

Diagnosis of ischemic small bowel disease by measurement of serum intestinal fatty acid-binding protein in patients with acute abdomen: a multicenter, observer-blinded validation study

Intestinal fatty acid-binding protein (I-FABP) is a low-molecular-mass (15 kDa) cytosolic protein found exclusively in the epithelial cells of the small bowel mucosa. We aimed to evaluate the clinical usefulness of serum I-FABP measurement for the diagnosis of ischemic small bowel disease. Patients with a clinical diagnosis of acute abdomen were recruited for this multicenter trial at one university hospital and nine city hospitals over a 13-month period. Serum I-FABP levels were measured in 361 eligible patients by an enzyme-linked immunosorbent assay using a specific monoclonal antibody. Of the 361 patients, 242 underwent surgery, and small bowel ischemia was diagnosed in 52 patients. The mean serum I-FABP level in the patients with small bowel ischemia was 40.7 ± 117.9 ng/ml, which was significantly higher than that in patients with non-ischemic small bowel disease (5.8 ± 15.6 ng/ml) and those with non-small bowel disease (1.8 ± 1.7 ng/ml). The serum I-FABP cutoff level for the diagnosis of small bowel ischemia was 3.1 ng/ml. Serum I-FABP was more efficient than conventional biochemical markers, in terms of sensitivity and positive and negative predictive values, in the diagnosis of small bowel ischemia. However, its specificity was slightly lower than that of creatinine phosphokinase or lactate dehydrogenase. The positive and negative likelihood ratios of serum I-FABP were 3.01 and 0.29, respectively. Serum I-FABP measurement is a non-invasive method that is potentially useful for the efficient identification of patients with acute abdomen who are at risk of small bowel ischemia.

Development of a High-specificity Sandwich ELISA System for the Quantification of Human Intestinal Fatty Acid-Binding Protein (I-FABP) Concentrations

Intestinal fatty acid-binding protein (I-FABP), a low molecular mass (approximately 15 kDa) cytoplasmic protein, is specifically located in epithelial cells of small bowel mucosal layer. This protein is rapidly released into the circulation after injury and/or destruction of these cells due to poor mesenteric blood flow and necrosis. Therefore, it can be used as a potential diagnostic biomarker for small bowel disease. In the present study, we have succeeded in developing a sandwich enzyme-linked immunosorbent assay (ELISA) system for quantification of human I-FABP. The range of sandwich ELISA system was 0.1–50 ng/mL of I-FABP in serum, and showed excellent quantitative characteristics such as reproducibility, dilution linearity, and recovery. No cross-reactivities were detected with other types of FABPs. As measured with this ELISA system, the serum I-FABP concentration was 1.1 ± 0.9 ng/mL in 61 healthy individuals, indicating that the reference value was below 2.0 ng/mL regardless of gender and age. Furthermore, mild abdominal pain or diarrhea before blood sampling did not affect I-FABP levels. Thus, this ELISA system could be used to accurately quantify human I-FABP concentrations in serum samples. These results suggest that it could be used as a new biomarker for the diagnosis of small bowel disease.

Intestinal fatty acid binding protein (I-FABP) as a possible biomarker of ileitis in patients with ulcerative colitis

BackgroundOne of nine types of FABP, intestinal fatty acid binding protein (I-FABP) is primarily limited to the mature enterocytes of the small intestine, with only trace amounts identified in the stomach and large intestine. The aim of this study was to investigate the use of I-FABP as a possible plasma marker of intestinal injury in patients with ulcerative colitis (UC). Material and methodsThe study group consisted of 42 patients (11 females and 31 males) with active ulcerative colitis (UC), aged from 24 to 74 years (mean age: 41.8±3.5 years). Plasma I-FABP concentrations and hsCRP were compared using endoscopic pictures scored according to the system developed by Meyers et al., and analysed in the context of inflammatory process extension: pancolitis, or distal or left side colitis. ResultsThe mean serum I-FABP concentration in UC patients was 166.9±36.3 vs. 61.3±7.8 pg/mL in healthy individuals. The highest I-FABP concentrations were observed in the pancolitis group (249.89±54.84 pg/mL), whereas individuals with left-side colitis had a mean I-FABP concentration of 61.8±8.5 pg/mL. Significant serum I-FABP elevation was observed in UC patients with a severe form of the disease, in contrast to the serum I-FABP concentration in patients with the mild form (260.5±60.6 vs. 61.5±7.9 pg/mL). ConclusionThe elevated serum I-FABP concentration in patients with UC may indicate ileitis. I-FABP may be a useful marker of the extended inflammatory process.

P0824 INTESTINAL FATTY ACID BINDING PROTEIN AND RISK OF ACUTE PANCREATITIS AFTER POSTERIOR SPINAL FUSION SURGERY

Introduction: Intestinal fatty acid binding protein (I-FABP) is a specific marker of enterocyte damage, and is a useful marker of intestinal ischemia/reperfusion. We previously reported that posterior spinal fusion in children is associated with early elevation of pro-inflammatory cytokines, and late postoperative complications such as acute pancreatitis (15–30%), sepsis (2–5%) and wound infection (5–8%). In this study we measured I-FABP levels at the end of surgery to see if this is a more specific marker for intestinal injury from ischemia/reperfusion and subsequent development of acute pancreatitis. Methods: After obtaining informed consent, children undergoing posterior spinal fusion were enrolled in an ongoing prospective study to identify markers predicting risk of post-operative complications. 7 who developed clinical acute pancreatitis and 9 matched controls were studied. Serum I-FABP was determined by using ELISA. Blood samples were taken at surgery start, and closure, and on post surgery day 1. Results: In most patients (13/16), I-FABP levels were elevated. I-FABP levels were significantly higher immediately post operative in those who subsequently developed pancreatitis vs. controls (343+/−320 pg/ml vs. 98.6+/−100.4 pg/ml, p<0.05). Indeed, 5/7 from pancreatitis, vs. 1/9 from Controls had levels >200 pg/ml ( OR=20, P<0.05). However, I-FABP levels were not associated with blood loss or systemic hypotension <55 mg Hg. Conclusion: Elevated I-FABP suggest that intestinal injury is common after posterior spinal fusion. Elevated I-FABP may be more specific than proinflammatory cytokines in predicting development of acute pancreatitis days later, and may prove to be a useful marker for intraoperative bowel ischemic injury.

LACK OF UTILITY OF INTESTINAL FATTY ACID BINDING PROTEIN LEVELS IN PREDICTING INTESTINAL ALLOGRAFT REJECTION

The enterocyte-specific protein, intestinal fatty acid binding protein (I-FABP), is detectable in serum only after intestinal injury. Previous studies in animals suggest that I-FABP might be a useful marker of intestinal allograft rejection. I-FABP was repetitively measured in nine intestinal transplant recipients and correlated with findings of surveillance endoscopy. Average interval between I-FABP determination and biopsy was 3.4 days (SD=4.2 days). Average number of rejection episodes per patient totalled 1.6+/-1.2. General linear modeling demonstrated no tendency for increases in serum FABP to precede histologic graft rejection (P=0.263). Restriction of the analysis to I-FABP determinations 1 day before or on the day of biopsy failed to affect these results. Minor increases in I-FABP were often associated with histologically normal grafts, whereas rejection often occurred when I-FABP was not detectable. Serum I-FABP levels do not predict clinical intestinal allograft rejection.

Small bowel allograft rejection detected by serum intestinal fatty acid-binding protein is reversible.

We hypothesized that, following experimental small bowel transplantation, immunosuppressive therapy initiated on the day of the initial rise in serum intestinal fatty acid-binding protein (I-FABP) would result in graft salvage. In previously published work, we showed that I-FABP was not detectable in the serum of isografted Lewis rats, but could be measured in the peripheral circulation during small bowel allograft rejection. A clinically useful method to monitor trans- planted allografts for rejection should detect the problem early in its evolution so that treatment to reverse the process would salvage a functional organ. Lewis rats served as recipients of LBNF1 out-of-continuity small bowel allografts and were studied in two groups: group I (control) received no immunosuppression and group II received cyclosporine (CsA, 15 mg/kg/d, p.o.) when I-FABP rose to > or = 80 ng/ml. Serum I-FABP was measured daily until the time of sacrifice. Full-thickness graft biopsies were obtained on postoperative days 3 (baseline), 6 or 7 (elevated I-FABP), 10, and 14 (sacrifice). Following transplantation baseline serum I-FABP (day 2 or 3) averaged < or = 10.0 ng/ml. I-FABP remained at baseline through day 5 (range 0-50 ng/ml) in all animals and then rose abruptly on either day 6 or 7 (range 86-150 ng/ml; P < 0.001 vs. baseline). Histology on day 6 or 7 revealed a mild-to-moderate cellular rejection. Cyclosporine therapy reversed the rejection reaction and restored the bowel to normal histology. Serum I-FABP returned to baseline. In untreated animals, serum I-FABP remained elevated for several days and then returned to baseline levels coincident with fulminant rejection and mucosal sloughing. I-FABP was released into the peripheral circulation early in the evolution of acute rejection in this model of small bowel transplantation. Immunosuppressive therapy initiated when elevated levels of I-FABP were detected in the serum resulted in graft salvage. Cyclosporine immunotherapy consistently reversed rejection in this model. This article represents the first report of salvage of small bowel allografts when immunosuppressive therapy was instituted prospectively on the basis of a serum marker. Immunoreactive I-FABP appears to hold significant potential as a biochemical screening tool for acute rejection occurring In small bowell allografts.

Intestinal fatty acid-binding protein is a useful diagnostic marker for mesenteric infarction in humans

BACKGROUND & AIMS: Acute ischemic diseases of the small bowel are lethal emergencies with no reliable diagnostic biochemical tests available. Experimental studies have suggested rat intestinal fatty acid-binding protein (I-FABP) as a serum marker reflecting bowel ischemia; the present study evaluates the human homologue (human I- FABP) as a serum marker for the diagnosis of acute ischemic diseases of the bowel. METHODS: Enzyme immunoassay was applied to determine I-FABP levels in the sera of 96 subjects: 13 preoperative patients with ischemic bowel diseases (5 cases of mesenteric infarction and 8 cases of strangulated obstruction of the small bowel), 35 healthy subjects, and 48 hospitalized patients with acute abdominal pain. RESULTS: Serum I-FABP levels were < 65 ng/mL in healthy subjects. In patients with acute abdominal pain, levels ranged from < 20 to 87 ng/mL (mean, 27.4 ng/mL), not significantly different from findings in healthy subjects. However, patients with ischemic bowel disease showed significantly higher I-FABP levels, ranging from < 20 to 1496 ng/mL (mean, 265.8 ng/mL). All 5 patients with mesenteric infarction showed I-FABP levels of > 100 ng/mL. CONCLUSIONS: I-FABP is a useful biochemical marker for the accurate diagnosis of mesenteric infarction. (Gastroenterology 1996 Feb;110(2):339-43)

Elevation of circulating intestinal fatty acid binding protein in a luminal contents-initiated model of NEC

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 ≤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 ≤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. Serum I-FABP may be a useful biochemical tool for the detection of mucosal damage in premature and stressed infants at risk for the development of NEC.