Intestinal Fatty Acid-binding Protein Levels Research Articles

Abnormal Distribution and Function of Circulating Monocytes and Enhanced Bacterial Translocation in Major Depressive Disorder.

Introduction: Major depressive disorder (MDD) patients experience a systemic inflammatory stage. Monocytes play an important role in innate inflammatory responses and may be modulated by bacterial translocation. Our aim was to investigate the subset distribution and function of circulating monocytes, levels of proinflammatory cytokines, gut barrier damage, and bacterial translocation in MDD patients.Methods: Twenty-two MDD patients without concomitant diseases and 14 sex- and age-matched healthy controls were studied. The levels of circulating CD14++CD16- (classical), CD14++CD16++ (intermediate) and CD14-CD16++ (nonclassical) monocytes and the intracytoplasmic tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 expression in the presence or absence of lipopolysaccharide (LPS) stimulation were analyzed by polychromatic flow cytometry. The serum TNF-α, IL-1β, IL-6, and IL-10 levels were measured by Luminex. LPS-binding protein (LBP), intestinal fatty acid-binding protein (I-FABP), and zonulin were measured by enzyme-linked immunosorbent assay (ELISA).Results: MDD patients had a significant increase in the frequency of intermediate monocytes and a significant decrease in the frequency of classical monocytes compared to those in the healthy controls. MDD patients had a significantly increased percentage of classical monocytes that expressed IL-1β, intermediate monocytes that expressed IL-1β and IL6 and nonclassical monocytes that expressed IL-1β, and decreased levels of nonclassical monocytes that expressed IL6 compared to those in the healthy controls. MDD patients had significantly increased levels of circulating TNF-α, IL-1β, LBP, and I-FABP compared to those in the healthy controls. MDD patients with high LBP levels had a significant reduction in the number of circulating monocytes compared to that in the normal-LBP MDD patients, which can be mainly ascribed to a decrease in the number of intermediate and nonclassical monocytes.Conclusions: We have demonstrated that compared to the healthy controls, MDD patients show a marked alteration in circulating monocytes, with an expansion of the intermediate subset with increased frequency of IL-1β and IL-6 producing cells. These patients also exhibited a systemic proinflammatory state, which was characterized by the enhanced serum TNF-α and IL-1β levels compared to those in the healthy controls. Furthermore, MDD patients showed increased LBP and I-FABP levels compared to those in healthy controls, indicating increased bacterial translocation and gut barrier damage.

Emodin regulates microRNA expressions of ileum in sepsis mice model

Objective To investigate the regulation of emodin on microRNA expressions in mouse model with sepsis by GeneChip microRNA array. Methods Forty two c57 mice were randomly (random number) divided into 3 groups: sham operation group (sham group, n=14),sepsis group(n=14) and emodin group (n=14). The sepsis model of the mouse was subjected to cecal ligation and puncture (CLP). Mice in emodin group received intraperitoneal injection of emodin (40 mg/kg) half an hour before operation and every 12 hours after CLP. All mice were sacrificed 48 h after surgery and part of the ileum were removed for intestine tissue stained with hematoxylin eosin. The levels of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6) and intestinal fatty acid binding protein (I-FABP) in peripheral blood were measured by enzyme-linked immunosorbent assay (ELISA). Total RNA of ileum tissues was extracted from the sepsis group and emodin group, and then subjected to miRNA microarray. The results of microarray were further verified by quantitative real-time PCR (qRT-PCR). Target genes of differentially expressed miRNAs were predicted and subjected to gene ontology (GO) and KEGG pathway enrichment analysis. Data of multi-groups were analyzed by one way variance (ANOVA) and inter-group comparisons were made by SNK-q tests. Mann-Whitney U test was used when homogeneity of variance were not met. The value of P<0.05 was considered statistically significant. Results Compared to the sepsis group, the levels of serum TNF-α, IL-6 and I-FABP in the emodin group were decreased significantly. MiRNA microarray showed that 23 miRNAs were differentially expressed in the emodin group as compared to the sepsis group, among which 17 miRNAs were up-regulated and 6 miRNAs were down-regulated. qRT-PCR results were consistent with miRNA array data. Target genes of 10 selected miRNAs were predicted and subjected to bioinformatic analysis. A total of 3 410 target genes were significantly enriched in 2 072 GO biological process terms, 246 GO cellular component items and 277 GO molecular function terms. Moreover, KEGG pathway analysis showed that these differential miRNAs were involved in the regulation of PI3K-Akt signaling pathway, MAPK signaling pathway, and TNF signaling pathway. Conclusions Emodin can regulate the expression of multiple microRNAs, and play an important role in protecting the intestinal mucosal barrier via a variety of targets and pathways. Key words: Emodin; Sepsis; Intestinal mucosa; MicroRNA; Expression profiles; Bioinformatics

Tobacco-Derived Lipopolysaccharide, Not Microbial Translocation, as a Potential Contributor to the Pathogenesis of Rheumatoid Arthritis.

Microbial lipopolysaccharides (LPS) have been implicated in the pathogenesis of rheumatoid arthritis (RA), possibly driving a systemic inflammatory response that may trigger the development and/or exacerbation of the disease. To explore the existence of this mechanism in African RA patients, we have measured systemic levels of LPS and its surrogate, LPS-binding protein (LBP), as well as those of intestinal fatty acid-binding protein (I-FABP), pulmonary surfactant protein D (SP-D), and cotinine in serum to identify possible origins of LPS, as well as associations of these biomarkers with rheumatoid factor (RF) and anticitrullinated peptide (aCCP) autoantibodies and the DAS 28-3 clinical disease severity score. A cohort of 40 disease-modifying antirheumatic drug-naïve, black South African RA patients rated by compound disease scores and 20 healthy subjects and 10 patients with chronic obstructive pulmonary disease (COPD) as controls were included in this study. Levels of the various biomarkers and autoantibodies were measured using a combination of ELISA and immunofluorimetric and immunoturbidometric procedures. LPS levels were lowest in the RA group compared to the healthy controls (p = 0.026) and COPD patients (p = 0.017), while LBP levels were also significantly lower in RA compared to the healthy individuals (p = 0.036). Levels of I-FABP and SP-D were comparable between all three groups. Categorisation of RA patients according to tobacco usage revealed the following significant positive correlations: LBP with C-reactive protein (p = 0.0137); a trend (p = 0.073) towards an association of LBP with the DAS 28-3 disease severity score; RF-IgG antibodies with both LPS and LBP (p = 0.033 and p = 0.041, respectively); aCCP-IgG antibodies with LPS (p = 0.044); and aCCP-IgG with RF-IgM autoantibodies (p = 0.0016). The findings of this study, several of them novel, imply that tobacco products, as opposed to microbial translocation, represent a potential source of LPS in this study cohort of RA patients, again underscoring the risks posed by tobacco usage for the development and severity of RA.

Non-immunological biomarkers for assessment of villous abnormalities in patients with celiac disease.

Demonstration of villous abnormalities is an essential component of diagnosis of celiac disease (CeD) that requires duodenal biopsies. There is a need for non-invasive biomarker(s) that can predict the presence of villous abnormalities. Levels of plasma citrulline, plasma intestinal fatty acid binding protein (I-FABP), and serum regenerating gene 1α (Reg1α) were estimated in treatment naïve patients with CeD and controls. The levels of these biomarkers and their cyclical pattern were validated in a predicted model of enteropathy. Optimum diagnostic cut-off values were derived, and the results were further validated in a prospective validation cohort. While level of plasma citrulline was significantly lower, the levels of plasma I-FABP and serum Reg1α were significantly higher in patients with CeD (n=131) in comparison with healthy (n=216) and disease controls (n=133), and their levels reversed after a gluten-free diet (GFD). In the model of predicted enteropathy (n=70), a sequential decrease and then increase in the level of plasma citrulline was observed; such a sequential change was not observed with I-FABP and Reg1α. The diagnostic accuracy for prediction of presence of villous abnormality was 89% and 78% if citrulline level was ≤30μM/L and I-FABP levels were ≥1100pg/mL, respectively. The results were validated in a prospective validation cohort (n=104) with a sensitivity and specificity of 79.5% and 83.1%, respectively, for predicting villous abnormalities of modified Marsh grade>2 at calculated cut-off values of citrulline and I-FABP. Plasma citrulline ≤30μM/L is the most consistent, highly reproducible non-invasive biomarker that can predict the presence of villous abnormality and has the potential for avoiding duodenal biopsies in 78% patients suspected to have CeD.

The Prognostic Value of Endotoxemia and Intestinal Barrier Biomarker ZO-1 in Bacteremic Sepsis

BackgroundIntestinal barrier dysfunction exerts a pivotal pathophysiological role in the development of multiple organ dysfunction in sepsis. The present study was undertaken to investigate the potential role of serum intestinal fatty acid-binding protein (I-FABP) and zonula occludens-1 (ZO-1) levels as biomarkers of intestinal barrier dysfunction in bacteremic sepsis. MethodsSeventy-five patients with bacteremic sepsis of abdominal origin (n = 34) or nonabdominal origin (n = 41) and 12 healthy controls were retrospectively studied. Blood samples collected upon sepsis diagnosis were analyzed for serum ZO-1, I-FABP and endotoxin levels. Prognostic scores Sequential Organ Failure Assessment (SOFA), quickSOFA and Acute Physiology and Chronic Health Evaluation (APACHE-II) were determined over the first 24 hours after sepsis diagnosis and patients’ outcome in terms of 28-day mortality was recorded. ResultsSerum ZO-1 levels were significantly higher in bacteremic septic patients as compared to controls with no difference between patients with abdominal or extra-abdominal source of infection. Serum I-FABP levels were significantly lower in septic patients as compared to control and this reduction was more evident in patients with bacteremic abdominal sepsis. Serum ZO-1 and endotoxin concentrations were found significantly higher in patients who did not survive from sepsis. In receiver operating characteristic curve analysis, both endotoxin and ZO-1 predicted 28-day mortality. In addition, ZO-1 and endotoxin were correlated with the prognostic scores of qSOFA, SOFA and APACHE II. ConclusionsThe results of this study indicate that serum ZO-1 might be a reliable biomarker of gut barrier dysfunction in sepsis, not affected by the abdominal or extra-abdominal site of infection. ZO-1, measured early at sepsis diagnosis, might represent a valuable additional prognostic tool for patients’ outcome.

Association between endotoxemia and enterocyte injury and clinical course in patients with gram-positive septic shock: A posthoc analysis of a prospective observational study.

Endotoxemia often occurs in patients with gram-positive infections. The possible mechanism is thought to be bacterial translocation after enterocyte hypoperfusion injury. However, the association between endotoxemia and enterocyte injury among patients with gram-positive septic shock has never been assessed. The aim of this study was to evaluate the association between endotoxemia and enterocyte injury in gram-positive septic shock patients and to evaluate the association among endotoxemia, subsequent clinical course, and other related factors.This was a posthoc analysis of a prospective observational study that evaluated the capability of intestinal fatty acid-binding protein (I-FABP), an indicator of enterocyte injury, to predict mortality. Among 57 patients in septic shock, those whose causative microorganisms were gram positive were included. The correlation between endotoxin activity (EA), which indicates endotoxemia, and I-FABP levels upon admission to the intensive care unit (ICU), the clinical course, and other related factors were evaluated.A total of 21 patients were examined. One-third of the patients presented with high EA levels at the time of ICU admission. However, there was no significant correlation between EA and I-FABP levels (Spearman ρ = 0.002, P = .993). Additionally, high EA levels were not associated with abdominal complications after ICU admission or mortality. Similarly, high EA levels were not associated with severity scores, inotropic scores, or lactate levels upon ICU admission, which were previously reported to be factors related to high EA levels.In this posthoc analysis, no correlation was observed between endotoxemia and enterocyte injury among patients in gram-positive septic shock. Additionally, high EA levels were not associated with the clinical course and reported factors related to endotoxemia. Although our results need to be validated in a large prospective cohort study, hypoperfusion enterocyte injury might not be a cause of endotoxemia in these patients. Thus, if there is no correlation between EA and I-FABP levels, other mechanisms that induce high EA levels among patients with gram-positive septic shock should be elucidated.

Serum Bovine Immunoglobulins Improve Inflammation and Gut Barrier Function in Persons with HIV and Enteropathy on Suppressive ART.

Background:Systemic inflammation persists in chronic HIV infection and is associated with increased rates of non-AIDS events such as cardiovascular and liver disease. Increased gut permeability and systemic exposure to microbial products are key drivers of this inflammation. Serum-derived bovine immunoglobulin/protein isolate (SBI) supports gut healing in other conditions such as inflammatory bowel disease.Methods:In this randomized, double-blind study, participants receiving suppressive antiretroviral therapy (ART) with chronic diarrhea received placebo or SBI at 2.5 g BID or 5 g BID for 4 weeks, followed by a 20-week placebo-free extension phase with SBI at either 2.5 or 5 g BID. Intestinal fatty acid binding protein (I-FABP), zonulin, flagellin, lipopolysaccharide (LPS) and LPS-binding protein, and inflammatory markers were measured by ELISA or multiplex assays. Non-parametric tests were used for analysis.Results:One hundred three participants completed the study. By week 24 SBI significantly decreased circulating levels of I-FABP (-0.35 ng/μL, P=0.002) and zonulin (-4.90 ng/μL, P=0.003), suggesting improvement in gut damage, and interleukin-6 (IL-6) (-0.40 pg/μL, P=0.002), reflecting improvement in systemic inflammation. In participants with the lowest quartile of CD4+ T-cell counts at baseline (189-418 cells/μL), CD4+ T-cell counts increased significantly (26 cells/μL; P=0.002).Conclusions:Oral SBI may decrease inflammation and warrants further exploration as a potential strategy to improve gut integrity and decrease systemic inflammation among persons receiving prolonged suppressive ART.

Clinical significance on serum intestinal fatty acid binding protein and D-lactic acid levels in early intestinal injury of patients with sepsis

To investigate the changes and clinical significances of intestinal fatty acid binding protein (I-FABP) and D-lactic acid levels in early intestinal injury of patients with sepsis and septic shock. A prospective observational study was conducted. Thirty septic patients (septic group) and 30 septic shock patients (septic shock group) were admitted to the intensive care unit (ICU) of General Hospital of Ningxia Medical University from August 2018 to December 2018, and 20 healthy adults were served as healthy control group. Serum samples were collected within 24 hours after ICU admission in septic shock and septic groups, and in healthy control group during physical examination. The serum I-FABP, D-lactic acid, endotoxin, hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and lactic acid (Lac) were determined. Gender and age of all subjects, and basic diseases, the main area of infection and acute physiology and chronic health evaluation II (APACHE II) scores within 24 hours after ICU admission of all patients were recorded. At the same time, the survival of the patients was followed up for 28 days. Spearman correlation analysis was used to analyze the correlation between serum I-FABP, D-lactic acid and other parameters. Risk factors of death in patients with sepsis and septic shock were screened by multivariate Logistic regression analysis of bicategorized variables. There was no significant difference in gender or age among the groups, as well as in the proportion of basic diseases, celiac infection or non-celiac infection between the sepsis group and the septic shock group, indicating that the general clinical baseline data among the groups were comparable. Serum levels of I-FABP and D-lactic acid in the sepsis group and the septic shock group were significantly higher than those in the healthy control group [I-FABP (μg/L): 27.46 (22.52, 34.39), 36.95 (29.82, 44.24) vs. 17.93 (14.65, 22.11), D-lactic acid (mg/L): 15.32 (9.84, 38.62), 27.95 (10.01, 47.69) vs. 9.38 (8.81, 14.48), all P < 0.01]. The serum level of I-FABP in the septic shock group was significantly higher than that in the sepsis group (P < 0.05), but the difference in serum D-lactic acid level between the two groups was not statistically significant (P > 0.05). Serum I-FABP level in the celiac infection group (n = 40) was significantly higher than that in the non-celiac infection group [n = 20; μg/L: 34.76 (27.46, 43.90) vs. 25.71 (20.55, 37.77), P < 0.01], but the difference in serum D-lactic acid level was not statistically significant [mg/L: 25.13 (9.83, 40.55) vs. 30.36 (10.17, 50.00), P > 0.05]. There was no significant difference in serum I-FABP or D-lactic acid levels between the survival group (n = 34) and the death group [n = 26; I-FABP (μg/L): 33.39 (25.20, 39.50) vs. 29.26 (22.50, 43.81), D-lactic acid (mg/L): 14.83 (9.71, 38.45) vs. 33.90 (11.93, 45.34), both P > 0.05]. Correlation analysis between serum I-FABP, D-lactic acid level and endotoxin, inflammatory factors, Lac and APACHE II score in septic and septic shock patients showed that only D-lactic acid was significantly positively correlated with TNF-α and Lac (r values were 0.455 and 0.406, respectively, both P < 0.01), while I-FABP was not correlated with endotoxin, inflammatory factors, Lac or APACHE II score. Multivariable Logistic regression analysis showed the APACHE II score was an independent risk factor to affect the prognosis (death for 28 days) of septic and septic shock patients [odds ratio (OR) = 1.248, 95% confidence interval (95%CI) = 1.091-1.427, P = 0.001], while I-FABP, D-lactic acid, endotoxin, hs-CRP, TNF-α, IL-6, and Lac had no impact on 28-day prognosis of patients. Serum I-FABP and D-lactic acid levels can evaluate early intestinal injury in patients with sepsis and septic shock, but neither of them is related to the prognosis of patients.

Preventive oral rehydration salts III could protect intestinal function in rats with exertional heatstroke

To observe the damage of various organs of rats with exertional heatstroke (EHS), and to investigate the protective effect of oral rehydration salts III (ORS III) on multi-organ function in rats with EHS. Fifty-one male Sprague-Dawley (SD) rats were randomly divided into four groups by random digit table: normal control group (n = 13), EHS group (n = 13), EHS+water group (n = 12), and EHS+ORS III group (n = 13). All rats in the EHS groups received adaptive training for 7 days before the experiment. On the 8th day, the rats of EHS+water and EHS+ORS III groups were orally given 20 mL/kg water or ORS III 30 minutes before the experiment. No pretreatment was performed in the EHS group. EHS model was reproduced by forcing rats to run under hot environment. The rats which refused to exercise and which core temperature > 40.5 centigrade were considered as the onset of EHS. The rats in the normal control group were exposed to room temperature (25±2) centigrade and humidity (50±5)% without any treatment. Six hours later, blood of inferior vena cava was collected, and the levels of serum MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH), alanine transaminase (ALT), aspartate transaminase (AST), serum creatinine (SCr), blood urea nitrogen (BUN), serum potassium, serum sodium and serum chloride were determined by automatic chemical analyzer. Serum intestinal fatty acid-binding protein (I-FABP) was determined by enzyme linked immunosorbent assay (ELISA). The levels of LDH, ALT, AST, BUN, serum sodium and serum chloride in the EHS group were significantly higher than those in the normal control group [LDH (U/L): 1 220±427 vs. 837±485, ALT (U/L): 138 (97, 164) vs. 37 (33, 42), AST (U/L): 409 (380, 566) vs. 86 (78, 104), BUN (mmol/L): 11.7 (9.6, 13.2) vs. 5.9 (5.5, 6.1), serum sodium (mmol/L): 148.0 (143.5, 154.5) vs. 139.0 (138.0, 140.5), serum chloride (mmol/L): 100.9±2.3 vs. 97.3±1.4, all P < 0.05], but no significant difference in CK-MB, SCr or serum potassium could be found [CK-MB (U/L): 1 280±373 vs. 1 379±480, SCr (μmol/L): 38.2±7.5 vs. 35.5±6.3, serum potassium (mmol/L): 5.5 (4.4, 6.2) vs. 4.7 (4.4, 4.9), all P > 0.05]. In the EHS+ORS III group, only serum potassium level was significantly lower than that in the EHS group [mmol/L: 4.0 (3.7, 4.4) vs. 5.5 (4.4, 6.2), P < 0.01], while no significant difference in other parameters was found between the EHS+ORS III group and the EHS group as well as the EHS+water group. Serum I-FABP level in the EHS group was significantly higher than that in the normal control group [μg/L: 36.90 (29.10, 45.00) vs. 11.39 (0.31, 20.80), P < 0.01]. Serum I-FABP level in the EHS+water and EHS+ORS III groups were notably lower than that in the EHS group [μg/L: 24.19 (20.00, 28.36), 0.31 (0.31, 5.58) vs. 36.90 (29.10, 45.00), both P < 0.01], additionally, I-FABP level was much lower in the EHS+ORS III group (P < 0.01). EHS could lead to liver, intestinal barrier dysfunction and electrolyte disturbance. Pre-treatment of ORS III could alleviate the intestinal dysfunction and electrolyte disorder caused by EHS in rats. It can lower the serum potassium to some extent. However, ORS III failed to protect liver from EHS.

Immune Activation and Microbial Translocation Markers in HIV-Exposed Uninfected Malawian Infants in the First Year of Life.

HIV-exposed uninfected (HEU) infants show a high rate of morbidity. We aimed to investigate on biomarkers of immune activation/microbial translocation in HEU infants, evaluating the impact that infections/malnutrition can have on biomarker levels during the first year of life. Clinical data of 72 Malawian infants were recorded monthly and correlated with levels of soluble CD14 (sCD14), lipopolysaccharide-binding protein (LBP) and intestinal fatty acid-binding protein (I-FABP), analyzed longitudinally. Levels of sCD14 and LBP showed a significant age-related increase. Higher levels of LBP (19.4 vs. 15.2 μg/ml) were associated with stunting, affecting 30% of the infants. The association remained statistically significant after adjusting for cytomegalovirus acquisition, malaria and respiratory infections (p = 0.031). I-FABP levels were significantly increased in infants experiencing gastrointestinal infections (1442.8 vs. 860.0 pg/ml, p = 0.018). We provide evidence that stunting is associated with an enhanced inflammatory response to microbial products in HEU children, suggesting that malnutrition status should be taken into consideration to better understand the alteration of the immune profile of HEU infants living in poor socioeconomic settings.

Calprotectin and Intestinal Fatty Acid Binding Protein (I-FABP) Level in Preterm Neonates with Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is inflammatory state of intestinal tissue which mostly occurred in preterm neonates and associated with ischemia and inflammation. This study was aimed to investigate calprotectin level (inflammatory marker) and intestinal fatty acid binding protein (I-FABP) (ischemia marker) in preterm neonates with NEC. This research was designed as cross sectional which involve 32 preterm neonates divided into 2 groups as follows: NEC group (n=16 subjects) and control group (n=16 subjects). Diagnosis of NEC was established by clinical and radiological signs (abdominal distension and pneumatosis). Fecal calprotectin and urinary I-FABP were measured using ELISA method. Results showed that fecal calprotectin and urinary I-FABP was significantly higher in NEC group as compared to control group ( Mann-Whitney test , p<0.05). Both calprotectin and I-FABP was positively correlated with NEC state (Spearman correlation test, p=0.000, r=0.866). Moreover, calprotectin and I-FABP level was positively correlated with grade (Bell’s classification) and type (Gordon’s classification) of NEC (Spearman correlation test, p<0.05). We concluded that calprotectin and I-FABP level was higher in NEC group. Moreover, I-FABP but not calprotectin, were correlated with grade and type of NEC.

Changes and significance of serum intestinal fatty acid binding protein in children with traumatic brain injury complicated with gastrointestinal dysfunction

Objective To study the changes and significance of serum intestinal fatty acid binding protein (IFABP) in children with traumatic brain injury(TBI) complicaled with acute gastrointestinal injury(AGI). Methods A total of 95 children suffering from TBI hospitalized in the PICU of the First Affiliated Hospital of Zhengzhou University from January 2017 to March 2018 were enrolled in the study.According to the modified Glasgow coma score combined with clinical classification criteria for acute closed head injury, the cases were devided into mild(43 cases), moderate (23 cases), and severe(29 cases). Children were graded according to AGI (AGI Ⅰ42 cases, AGI Ⅱ 30 cases, AGI Ⅲ 13 cases, and AGI Ⅳ 10 cases). Thirty healthy children who underwent physical examination at outpatient service were enrolled as the control group.Blood samples were collected at the time of admission and on the 3rd day after admission.Serum IFABP was detected by ELISA, and the differences of serum IFABP concentrations were compared among groups.The correlations between IFABP with TBI classification and AGI grade were analyzed.The receiver operating characteristic (ROC) curve was drawn, and the predictive values of IFABP for the diagnosis of children with TBI complicated with AGI were evaluated. Results On the day of admission, the serum levels of IFABP in mild, moderate and severe brain injury group were significantly higher than that in control group (all P<0.01). And serum IFABP concentration gradually increased with the increase of brain injury (all P<0.01). Serum IFABP levels in children with AGI grade Ⅰto Ⅳ were significantly higher than those in control group (all P<0.01). The levels of serum IFABP also increased with the increase of AGI level (all P<0.01). The concentration of serum IFABP was positively correlated with the grade of TBI and AGI (rs=0.82, P<0.01; rs=0.70, P<0.01). In each group, the levels of serum IFABP on the 3rd day after admission were lower than those on admission (all P<0.01). The ROC curve analysis showed that serum IFABP was of high diagnostic value in children with TBI complicated with AGI, and the area under the ROC curve was 0.88.When the cutoff value of IFABP was 431.36 ng/L, the sensitivity and specificity were 71.61% and 90.00%, respectively. Conclusion Serum IFABP can be used as a sensitive indicator for the early diagnosis and disease assessment in children with TBI complicated with gastrointestinal dysfunction. Key words: Intestinal fatty acid binding protein; Traumatic brain injury; Gastrointestinal dysfunction; Children

Intestinal fatty acid binding protein (I-FABP) as a marker for acute intestinal ischemia

Background: Acute mesenteric ischemia accounts for around 0.1% of all hospital admission and less than 1% of emergency admissions. However, the presentation is varied, and diagnosis is obscure. The diagnosis of intestinal ischemia demands a high index of suspicion. The overall mortality associated with mesenteric ischemia is between 60% and 93% but rises acutely once bowel wall infarction has occurred. Early diagnosis of ischemia remains the key to reduce morbidity and mortality. I-FABP is a cytosolic protein present in epithelial cells of intestines and released upon ischemia or necrosis of bowel. Author estimated the levels of I-FABP in serum and established it as a marker for acute intestinal ischemia.Methods: 40 patients admitted to JSS Hospital with suspected acute intestinal ischemia were included in the study. Plasma concentrations were quantified using ELISA for fatty acid binding protein 2. Statistical methods were applied and sensitivity and specificity of serum I-FABP were determined. Confirmation of ischemia was by histopathological analysis of the resected bowel specimen.Results: 23 patients out of the 40 were diagnosed to have intestinal ischemia. Mean values of serum IFABP levels were significantly higher in patients diagnosed with intestinal ischemia (65.94pg/ml in the non-ischemic group vs 673.53pg/ml in the ischemic group P=0.0002). Cut off chosen in diagnosing intestinal ischemia in this study was 187.59pg/ml. Sensitivity was 95.7% and specificity 88%.Conclusions: Serum I-FABP can be used for the diagnosis for intestinal ischemia. It is specific and sensitive marker to detect early bowel ischemia.

The intestinal fatty acid-binding protein as a marker for intestinal damage in gastroschisis.

Background/PurposeWe analyzed the capacity of urinary Intestinal fatty acid-binding protein (I-FABP) to quantify the degree of mucosal injury in neonates with gastroschisis (GS) and to predict the speed of their clinical recovery after surgery.MethodsIn this prospective study, we collected urine during the first 48h after surgery from neonates operated between 2012 and 2015 for GS. Neonates with surgery that did not include gut mucosa served as controls for simple GS and neonates with surgery for intestinal atresia served as control for complex GS patients. The I-FABP levels were analyzed by ELISA.ResultsUrinary I-FABP after the surgery is significantly higher in GS newborns than in control group; I-FABP in complex GS is higher than in simple GS. I-FABP can predict subsequent operation for ileus in patients with complex GS. Both ways of abdominal wall closure (i.e. primary closure and stepwise reconstruction) led to similar levels of I-FABP. None of the static I-FABP values was useful for the outcome prediction. The steep decrease in I-FABP after the surgery is associated with faster recovery, but it cannot predict early start of minimal enteral feeding, full enteral feeding or length of hospitalization.ConclusionUrinary I-FABP reflects the mucosal damage in gastroschisis but it has only a limited predictive value for patients’ outcome.

Association Between Macroscopic Tongue Ischemia and Enterocyte Injury and Poor Outcome in Patients With Septic Shock: A Preliminary Observational Study.

A correlation between sublingual and intestinal mucosa microcirculation, and ischemic necrosis of the tongue as a sign of poor prognosis has been reported. However, an association between tongue ischemia and intestinal health and subsequent outcome has never been studied. This preliminary prospective observational study evaluated the association between macroscopic tongue ischemia and enterocyte injury and poor outcome in patients with septic shock. In this study, 57 adults with septic shock on mechanical ventilators were enrolled. Macroscopic tongue ischemia upon intensive care unit (ICU) admission was assessed by two independent intensivists. We used intestinal fatty-acid binding protein (I-FABP) as a biomarker of enterocyte injury and evaluated the association with tongue ischemia. Demographic variables, risk factor data, and 28-day mortality information were also collected. Compared with patients with normal tongues (n = 45), those with ischemic tongues (n = 12) had a significantly higher Acute Physiology and Chronic Health Evaluation II score (29.0 [25.0-34.0] vs. 36.5 [30.5-44.5], P = 0.017), lactate level (2.8 [2.0-5.0] vs. 9.3 [4.5-10.6], P = 0.002), and I-FABP level (1.9 [0.8-4.0] vs. 54.4 [19.5-159.3], P < 0.001) and the all-cause 28-day mortality was significantly higher (7% vs. 83%, P < 0.001). In conclusion, macroscopic tongue ischemia at ICU admission was associated with enterocyte injury and poor outcome in patients with septic shock. Although there is a disadvantage in that assessment of the tongue was subjective, tongue ischemia could be used to gauge the severity of intestinal injury and to estimate poor outcome in the clinical setting.

Intestinal fatty acid-binding protein as a predictor of prognosis in postoperative cardiac surgery patients.

During the perioperative period of cardiac disease, as many risk factors exist, such as primary cardiac diseases, the use of vasopressors, ischemia-reperfusion injury during cardiopulmonary bypass (CPB), and surgical stress, the gut suffered from ischemia, anoxia and oxidative stress, which would lead to the enterocyte injury. The aim of this study was to explore whether serum intestinal fatty acid-binding protein (IFABP), which is excreted specifically from damaged intestinal enterocytes, as a predictor of prognosis in postoperative cardiac surgery patients.From January 2017 to December 2017, 40 postoperative cardiac surgery patients were enrolled in this observational study. Serum IFABP levels and prognostic biomarkers were recorded at intensive care unit (ICU) admission.The serum IFABP levels were significantly higher in postoperative cardiac surgery patients who complicated with multiple organ dysfunction syndrome (MODS) (median, 883.20 pg/mL vs 426.10 pg/mL; P < .001), infective complications (median, 917.70 pg/mL vs 409.40 pg/mL; P < .001), or who stayed in ICU beyond 4 days (median, 807.65 pg/mL vs 426.10 pg/mL; P < .001). Moreover, in patients who suffered from right ventricular dysfunction, the serum IFABP levels were significantly higher (median, 737.85 pg/mL vs 445.55 pg/mL; P = .016). The serum IFABP levels also showed great precision for the prediction of MODS (the area under curve, AUC 0.923), infective complications (AUC 0.961) and ICU stay beyond 4 days (AUC 0.853). And it correlated significantly with the acute physiology and chronic health evaluation (APACHE) II score (P < .05), sequential organ failure assessment (SOFA) score (P < .05), and acute gastrointestinal injury (AGI) grade (P < .001).The serum IFABP level at ICU admission is a valuable, convenient, and objective early predictor of prognosis in postoperative cardiac surgery patients.

DIAGNOSTIC VALUE OF INTESTINAL FATTY ACID-BINDING PROTEIN (I-FABP) IN PRETERM INFANTS WITH NECROTIZING ENTEROCOLITIS

Introduction. Necrotizing enterocolitis (NEC) is characterized by loss of gut wall integrity. Fatty acid binding protein (I-FABP) in blood serum allows to isolate infants in the early stages of the NEC and correlates with the severity of the disease. This protein is involved in the transport of polar lipids, such as fatty acids from the lumen of the small intestine.Aim of work: to determine diagnostic value of fatty acid binding protein (I-FABP) in blood serum in preterm children with necrotizing enterocolitis.Materials and methods. Under supervision there were 67 preterm children with NEC. The children were divided into groups depending on the severity of the NEC. Prior to the first group were involved 20 preterm infants with the NEC of IA and IB stage, and to the second group were involved 30 premature infants from the NEC of IIA and IIB stage and to the third group were involved 7 preterm infants with NEC of IIIA stage. The control group comprised 10 preterm infants without NEC. The content of the protein bound to fatty acids, the intestinal form (I-FABP) in serum was determined by the immunoassay method of the Human I-FABP (Hycult Biotech, Netherlands) kit according to the manufacturer's instructions.Results and discussion. Children of the III group had significantly lower body mass (p&lt;0.05) and gestational period at birth than children of the control group.All children with NEC involved in the study had an increase in the serum I-FABP content. Thus, in the I group, the I-FABP content was 796,0 [579-961] pg/ml, in group II - 1031,0 [873-1630] pg/ml, in group IІІ - 1698,0 [1598-2953] pg/ml, which significantly exceeded the value of I-FABP in control group children - 269,5 [252-289] pg/ml (p&lt;0.05). Also, there was a significant difference in I-FABP content in preterm infants with NEC, depending on the severity of the disease, the higher the stage, the higher the I-FABP content (p&lt;0.05). Diagnostic value of I-FABP in blood serum of prematurely born children with necrotizing enterocolitis, depending on severity, determined by ROC analysis. The most diagnostic value of I-FABP is for the diagnosis of NEC grade III. I-FABP ≥ 1484.0 pg/ml allows to identify NEC of III stage in preterm children with a sensitivity of 85.7% and a specificity of 82.0%. The area under the curve (AUC) is 0.880 [95% CI 0.784-0.976], which indicates a high diagnostic value of the model.Conclusions. The heavier course of NEC is associated with lower body weight (p&lt;0.05) and lower gestational age. In all children who were born prematurely with necrotizing enterocolitis, the content of intestinal fatty acid-binding protein (I-FABP) in serum was elevated. The highest level of I-FABP (1698,0 [1598-2953] pg/ml) was observed in preterm infants with necrotizing enterocolitis of the third stage (p&lt;0.05). The I-FABP index ≥1484.0 pg/ml allows to identify preterm infants with necrotizing enterocolitis of III stage with a sensitivity of 85.7% and a specificity of 82.0%, the area under the curve 0.880 [95% CI 0.784-0.976], which confirms the results of the ROC analysis.

Intestinal fatty acid–binding protein levels in patients with chronic renal failure

BackgroundIntestinal fatty acid–binding protein (I-FABP), a biomarker of enterocyte injury, has been reported to be a diagnostic marker of intestinal ischemia and a prognostic marker in critically ill patients. However, the kinetics of I-FABP in renal failure patients is unknown. We sought to identify I-FABP levels in patients with chronic kidney disease (CKD) and end-stage kidney disease (ESKD) on hemodialysis (HD) and to identify the manner in which the I-FABP levels change. Materials and methodsAdult patients who were admitted for elective cardiac surgery with either normal renal function (NRF), CKD, or ESKD on HD were enrolled. Serum I-FABP levels in NRF and CKD patients and in ESKD patients before and after HD were determined. ResultsA total of 124 patients were evaluated: 47 NRF, 53 CKD, and 24 ESKD. The I-FABP levels of the CKD patients and pre-HD ESKD patients were significantly higher than those of the NRF patients (P = 0.018 and P <0.001, respectively). I-FABP levels were significantly negatively correlated with the estimated glomerular filtration rate in NRF and CKD patients (Spearman's ρ = −0.313, P = 0.002). In addition, I-FABP levels in ESKD patients were significantly lower after HD than those before HD (P <0.001). ConclusionsI-FABP levels in CKD and pre-HD ESKD patients were significantly higher than those in NRF patients. In addition, I-FABP was significantly eliminated by HD in patients with ESKD. Clinicians and researchers should consider this aspect of I-FABP when using it as a diagnostic and prognostic marker in patients with renal insufficiency.

Serum intestinal fatty acid-binding protein in the noninvasive diagnosis of celiac disease.

Current diagnostic guidelines for celiac disease (CD) in pediatric patients require a duodenal biopsy if the IgA anti-tissue transglutaminase (tTG) is below 10x the upper limit of normal (ULN). Additional markers may enable a noninvasive diagnosis in this group. Serum intestinal-fatty acid-binding protein (I-FABP), a marker for intestinal epithelial damage, could be useful in this respect. A total of 95 children with a clinical suspicion of CD and tTG 1-10x ULN were investigated. All had a duodenal biopsy and analysis of serum I-FABP. A control group of 161 children with familial short stature and normal tTG was included. I-FABP levels in the 71 patients with tTG 1-10x ULN and biopsy-proven CD (median 725pg/mL) were not significantly different (p=0.13) from the levels in the 24 patients with a tTG 1-10x ULN but a normal biopsy (median 497pg/mL). However, when combining tTG and I-FABP levels, 11/24 patients could have been diagnosed noninvasively if tTG is ≥ 50 U/mL and I-FABP ≥880pg/mL or in 12/19 patients if tTG is ≥ 60 U/mL and I-FABP ≥ 620pg/mL. Therefore, addition of I-FABP to the diagnostic procedure of CD may provide a noninvasive diagnosis in patients with a tTG ≥ 50 U/mL.

Doppler-guided goal-directed fluid therapy does not affect intestinal cell damage but increases global gastrointestinal perfusion in colorectal surgery: a randomized controlled trial.

Individualized, goal-directed fluid therapy (GDFT), based on Doppler measurements of stroke volume, has been proposed as a treatment strategy in terms of reducing complications, mortality and length of hospital stay in major bowel surgery. We studied the effect of Doppler-guided GDFT on intestinal damage as compared with standard postoperative fluid replacement. Patients undergoing elective colorectal resection for malignancy were randomized either to standard intra- and postoperative fluid therapy or to standard fluid therapy with additional Doppler-guided GDFT. The primary outcome was intestinal epithelial cell damage measured by plasma levels of intestinal fatty acid-binding protein (I-FABP). Global gastrointestinal perfusion was measured by gastric tonometry, expressed as regional (gastric) minus arterial CO2 -gap (Pr-a CO2 -gap). I-FABP levels were not significantly different between the intervention group and the control group (respectively, 440.8 (251.6) pg/ml and 522.4 (759.9) pg/ml, P=0.67). Mean areas under the curve (AUCs) of intra-operative Pr-a CO2 -gaps were significantly lower in the intervention group than in the control group (P=0.01), indicating better global gastrointestinal perfusion in the intervention group. Moreover, the mean intra-operative Pr-a CO2 -gap peak in the intervention group was 0.5 (1.0) kPa, which was significantly lower than the mean peak in the control group, of 1.4 (1.4) kPa (P=0.03). Doppler-guided GDFT during and in the first hours after elective colorectal surgery for malignancy increases global gastrointestinal perfusion, as measured by Pr-a CO2 -gap.