Serum Calprotectin in the Evaluation of Gastrointestinal Diseases: An Ace up Your Sleeve?

Background: Calprotectin (CP) is a calcium- and zinc-binding protein that plays a key role in innate immunity and in the recruitment of inflammatory cells. CP can be detected both in serum and in fecal samples. Serum CP (sCP) is more specific for autoimmune diseases, while fecal CP (fCP) has been well investigated for gastrointestinal diseases. Few studies have shown the clinical effectiveness of sCP as an acute-phase biomarker for gastrointestinal diseases. Aim: The aim of this narrative review is to discuss the role of sCP as a useful alternative biomarker of the acute-phase activity of gastrointestinal diseases and as a possible tool for screening and monitoring these diseases. Material and Methods: We searched original articles, abstracts, reviews, case reports, and clinical trials on PubMed®, Up-to-Date®, and Medscape® in the last ten years. Conclusion: We found that sCP could represent a useful biomarker in the evaluation of the inflammatory stage in patients with immune-mediated gastrointestinal diseases, but more studies are needed to promote its routine use in clinical practice as a diagnostic and prognostic biomarker as a replacement for fCP.

Functional Gastrointestinal Symptoms in Children with Autism and ADHD: Profiles of Hair and Salivary Cortisol, Serum Leptin Concentrations and Externalizing/Internalizing Problems.

BACKGROUND: Functional Gastrointestinal Disorders (FGIDs) present a higher prevalence in individuals with Neurodevelopmental Disorders (NDDs). The Stress System and the Gut-Brain axis (GBA) may mediate these relations. We aimed to assess the prevalence and profile of FGIDs in a clinical sample of children with Autism Spectrum Disorder (ASD) and Attention Deficit/Hyperactivity Disorder (ADHD) compared to typically developing children (TD) as well as to investigate possible relations between stress-related biomarkers and internalizing/externalizing problems in children with NDDS. METHODS: In total, 120 children, aged between 4 and 12 years old, formed three groups (N = 40, each): ADHD, ASD and TD. Salivary cortisol, hair cortisol and serum leptin were measured. RESULTS: The ASD group had more FGID problems than the TD group (p = 0.001). The ADHD and ASD groups had higher total internalizing/externalizing problems than the TD group (p < 0.0001, p < 0.0001, p = 0.005, respectively). Children with FGIDs showed more total, internalizing and externalizing problems compared to children without FGIDs (p < 0.0001, p < 0.0001, p = 0.041, respectively). The ADHD group showed lower AUCg values (p < 0.0001), while the hair cortisol was higher for the TD group (p < 0.0001). CONCLUSION: In conclusion, children with NDDs had more FGID symptoms and present higher internalizing and externalizing problems. Children with ADHD and FGIDs had more internalizing problems compared to those without FGIDs. No differences in stress-related biomarkers were shown to differentiate children with NDDs with and without FGIDs. Future prospective studies including a greater number of children may elucidate the biological pathways linking these comorbidities.

Evaluation of gastrointestinal tract lesions and serum malondialdehyde levels after repeated oral administration of phenylbutazone in horses.

Phenylbutazone (PBZ) is a widely used nonsteroidal anti-inflammatory drug for horses. However, because of its gastrointestinal side effects, its administration requires careful attention in veterinary practice. Malondialdehyde (MDA) is a serum biomarker associated with increased damage to the equine gastrointestinal system. This study investigated the hematological effects and alterations in the gastrointestinal tract and assessed serum MDA concentrations following repeated oral PBZ administration at clinical doses. Fourteen horses were randomly divided into control and treatment groups. All horses in the treatment group were administered 4.4 milligrams per kilogram of body weight of PBZ syrup orally twice a day for 7 days, whereas the control group received syrup as a placebo. The development of gastrointestinal side effects was investigated using gastroscopy, abdominal ultrasound, and fecal pH; serum MDA concentrations were assessed using a commercially available enzyme-linked immunosorbent assay kit. Data were compared between PBZ-treated and control horses before and after the treatment period. The treatment group exhibited decreased albumin and total protein concentrations. Moreover, this group exhibited a higher thickness of the right dorsal colon wall (p = 0.03) and had higher scores for squamous gastric ulcers (p = 0.01). Fecal pH was lower in the treatment group than in the control group after PBZ administration (p < 0.01). Although MDA concentrations were higher in the treatment group after PBZ administration, they did not differ significantly from those of the control group. This study highlighted the changes in hematological and gastrointestinal lesions resulting from PBZ administration in horses at clinical doses, even without clinical signs. However, MDA may not be an optimal biomarker for the early detection of gastrointestinal damage due to PBZ treatment in horses.

Intestinal Fatty Acid-Binding Protein as a Potential Biomarker for Gastrointestinal Complications after Complex Endovascular Aortic Surgery.

BACKGROUND: This study aimed to investigate the association between intestinal fatty acid-binding protein (I-FABP), acute gastrointestinal injury (AGI) grade, and gastrointestinal (GI) complications after fenestrated or branched endovascular aortic aneurysm repair. METHODS: A total of 17 patients undergoing endovascular aortic repair for thoracoabdominal, juxtarenal, suprarenal, or pararenal aneurysm between May 2017 and September 2018 were enrolled. Blood samples were collected preoperatively and during postoperative intensive care. The blood samples were analyzed for I-FABP with enzyme-linked immunosorbent assay. Gastrointestinal function was assessed according to the AGI grade every day during postoperative intensive care. RESULTS: Higher concentrations of I-FABP at 24 hr and 48 hr correlated to higher AGI grade on postoperative days 1, 2, and 3 (P = 0.032 and P = 0.048, P = 0.040 and P = 0.018, and P = 0.012 and P = 0.016, respectively). Patients who developed a GI complication within 90 days postoperatively had a higher overall AGI grade than those who did not develop a GI complication (P < 0.001), as well as higher concentrations of I-FABP at 48 hrs (P = 0.019). Patients developing GI dysfunction (AGI grade ≥2) had a higher frequency of complications (P = 0.009) and longer length of stay in the intensive care unit (P = 0.008). CONCLUSIONS: In patients undergoing endovascular aortic repair for complex aneurysm increased postoperative plasma I-FABP concentrations and postoperative GI dysfunction, evaluated using the AGI grade, were associated with GI complications, indicating that these measures may be useful in the postoperative management of these patients.

The effect of feeding on serum concentrations of cobalamin, folate, trypsin-like immunoreactivity, and pancreatic lipase immunoreactivity in dogs with signs of chronic gastrointestinal disease.

BACKGROUND: It is unknown if serum concentrations of cobalamin, folate, canine pancreatic lipase immunoreactivity (cPLI), and canine trypsin-like immunoreactivity (cTLI) obtained postprandially are equivalent to measurements obtained after withholding food in dogs with suspected gastrointestinal disease. HYPOTHESIS/OBJECTIVES: Measurements of serum concentrations of cobalamin, folate, cPLI, and cTLI postprandially will be equivalent to measurements after 12 hours of withholding food in dogs with signs of chronic gastrointestinal disease. Changes observed will not alter clinical interpretation. ANIMALS: 51 client-owned dogs with signs of gastrointestinal disease. METHODS: Prospective single arm clinical trial. Serum concentrations of cobalamin, folate, cPLI and cTLI 2, 4, and 8 hours postprandially were compared by equivalence testing to values after withholding food for 12 hours (baseline). RESULTS: Mean serum cobalamin concentrations 2 hours (498.1 ± 213.1 ng/L; P = 0.024) and 4 hours (501.9 ± 207.4 ng/L; P = 0.008) postprandial were equivalent to baseline (517.3 ± 211.5 ng/L). Mean serum cTLI 2 hours (31.3 ± 14 µg/L; P < 0.001) and 4 hours (29.6 ± 13.1 µg/L; P = 0.027) postprandial were equivalent to baseline (31.1 ± 15 µg/L). Mean serum folate concentration 2 hours postprandial (15 ± 7.7 µg/L) was equivalent to baseline (13.7 ± 8.3 µg/L; P < 0.001). Equivalence could not be assessed for cPLI due to results below the lower limit of quantification. Feeding altered the clinical interpretation in 27% (cobalamin), 35% (folate), 20% (cTLI), and 12% (cPLI) of dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: The clinical interpretation for a substantial number of samples changed after feeding, therefore withholding food before sample collection is prudent.

Development of a plasma maltose assay method as a screening test for upper gastrointestinal disorders.

BACKGROUND AND OBJECTIVE: The disaccharide loading test is a method to assess gastric mucosal damage. Since Trelan-G75, which is used for the sugar tolerance test, contains disaccharide maltose, if maltose is detected at a high sensitivity in the sample blood used in the sugar tolerance test, screening for upper gastrointestinal mucosal damage can be made simultaneously with the sugar tolerance test for the diagnosis of diabetes. METHODS: Glucose-6-phosphate is generated by treating maltose with maltose phosphorylase, ß-phosphoglucomutase, and glucose-1,6-bisphosphate. Then, change in the absorbance at 405 nm is measured by the enzymatic cycling method using Thio-NADP, ß-NADPH, and Glucose-6-phosphate dehydrogenase. After evaluating the optimal condition for this method, it is mounted on an automatic biochemical analyzer, and samples after the sugar tolerance test were assayed. RESULTS: Regarding the performance of this method, the repeatability was 10-50 µmol/L with a CV of ≤1.1%. Concerning the assay range, a curve passing the origin with a range of linearity up to 120 µmol/L was obtained. No effect of dyes or sugars in the blood was noted. As a result of application to patients with gastric mucosal disorders (those who had a health checkup), significant differences were observed depending on the stage of atrophic gastritis. DISCUSSION: This method has a high sensitivity and a high precision and can be used for high-speed analysis on an automatic analyzer. It has the potential to be used as a screening test for gastric mucosal damage.

Serum gastrin and pepsinogen I, II concentrations in children with Helicobacter pylori infection: the role of CagA and VacA

Serum gastrin and pepsinogen concentrations were measured in 51 children infected with Helicobacter pylori, to investigate the clinical significance and influence of CagA and VacA on serum concentrations of these peptides. CagA+ was 44/51 (86%) and VacA+ was 42/51 (82%). Type I (CagA+/VacA+) included 39/51 (76%), type II (CagA-/VacA-) was 4/51 (8%), and intermediate (CagA-/VacA+, CagA+/VacA-) was 8/51 (16%). There was no significant correlation between endoscopic diagnosis and the state of CagA/VacA. Serum gastrin concentrations were not significantly correlated with the state of CagA/VacA. Serum pepsinogen I and II concentrations were significantly higher in CagA+ than in CagA-, but there was no significant difference between VacA+ and VacA-, Serum pepsinogen I/II ratio was not significantly correlated with the state of CagA/VacA. There was no significant difference between serum concentrations of gastrin, pepsinogen I and H. pylori phenotypes. However, pepsinogen II concentration was significantly higher in type I than type II. Pepsinogen I/II ratio was significantly lower in type I and intermediate than in type II. These findings suggest that CagA positively and phenotype of H. pylori could play a role in the development of upper gastrointestinal diseases in children.

A survey of parasites in primary school children in Dominica, West Indies

A study of Dominican school children aged four to twelve years showed that infection with gastrointestinal parasites was very common. Trichuris was found in the stools in 92 percent of the children. Ascaris in 38 percent, Nectar in 11 percent, Giardia in 18 percent and E. histolytica in 1 percent. In spite of the high prevalence of parasites, the general health of children studied was remarkably good, and only 18 of the 1000 children were found to have a haemoglobin level below 10g/dl (Summary)