Outcome of Lactoferrin Supplementation In Critically Ill Septic Children With Acute Gut Failure

Background Sepsis is a clinical syndrome caused by many infections. Septic patients may suffer from Gut failure resulting in severe complications. To improve Gut function, the effect of lactofferin supplementation has been studied. Objective To test the effect of lactoferrin supplementation on improving gut barrier function by using plasma citrulline level as a marker of functional enterocytic mass. Patients and Methods This double armed single blinded therapeutic clinical trial study was conducted on 40 children admitted to (PICUs) of Ain Shams University Hospitals. By diagnosis sepsis and gut failure, twenty of them weren't supplemented with LF (group 1) and the other twenty were supplemented (group 2). All critically ill septic patients diagnosed with acute gut failure admitted from October 2018 to 2019 were subjected to citrulline level measurement by (ELISA). Results We found that citrulline concentration was significantly lower in patients (9.52 nmol/L) than control group (122 nmol/L) and lowered in non survivors (5.13 nmol/L) than survivors (30.68 nmol/L) with p value of 0.027 and 0.034 respectively and a cut off value ≤ 7.82 mmol/L. There was no significant difference between the groups 1 and 2 in treatment of sepsis with gut failure. Conclusion (1) Citrulline level can be used as a predictor of intestinal failure severity and mortality. (2) Lactoferrin supplementation was not beneficial in pediatric septic patient with gut failure and did not improve outcome or prognosis of patients.

Plasma Citrulline Level In Preterm Neonates With Necrotizing Enterocolitis

Background Necrotizing enterocolitis is a leading cause of mortality and morbidity in preterm neonates, lacks a reliable biomarker. Citrulline is primarily produced by enterocytes and correlates with intestinal function. Objective of the study is to test if Citrulline can be used as a biomarker of NEC and serving as a biomarker for intestinal recovery. Subjects This is a case control study, Plasma citrulline levels of neonates with a gestational age <35 weeks and 2000 gram who developed NEC were measured, comparing it to properly gestational age and weight matched pretrem neonates. Patients and methods sixty neonates were classified into two groups: the patients group which included 30 neonates with confirmed NEC and the control group which included 30 healthy preterm neonates. Results Plasma citrulline level was significantly lower in the patients group than in the control group With Median citrulline levels of NEC and control groups were 2 and 20 μmol/l respectively (P < 0.0001), with a sensitivity of 86.7%, specificity of 93.3% and cut off level of citrulline was ≤11μmol/l for diagnosis. Conclusion Plasma citrulline level is a very good non invasive marker for NEC diagnosis.

Citrulline as a biomarker of short bowel syndrome in children

Purpose. To determine the diagnostic significance of blood citrulline level when estimating the short bowel syndrome (SBS) in children under 5 years old. To determine the blood citrulline level in children of different age. Methods. The examined group (N=31) included children under 5 who underwent small or small and large intestine resection and developed (15 children) or not developed (16 children) clinical signs of SBS. The control group included children who underwent no surgery on the GIT and had no congenital malformations and clinical signs of enteropathy (N=42). To determine the level of citrulline, overpressured high performance liquid column chromatography was used. Statistical analysis of the results was done with MedCalc® version 18.11.3. Results. Mean level of blood citrulline is 28.9 µmol/l in the examined group (95% CI 23.2–34.6) and 30.5 µmol/l in the control group (95% CI 25.0–35.1). Reliable data of the ratio between blood level citrulline and age of the child were obtained both among operated and non-operated children. The odds ratio of determining citrulline in blood was below 24.4 µmol/l in development of SBS clinical picture and amounted to 4.08 р < 0,05. Additional use of ROC analysis confirms the presence of interrelation between citrulline level and absence or presence of SBS clinical signs with 100% specificity and 43% sensitivity. The area under curve (categorical variable showing whether SBS is present or lacking) is 0,746, р = 0,005. Conclusion. Determination of serum citrulline as a diagnostic marker of short bowel syndrome in children under 5 found low sensitivity but high specificity. Thus, blood citrulline index can be used as a biomarker to diagnose SBS, to describe the course of SBS in detail and determine the risk of severe forms of this pathology in children under 5.

The Correlation of L-citrulline Levels with Blood Pressure in Severe Preeclampsia

BACKGROUND: Based on 'vascular disorder of pregnancy' terminology, preeclampsia primarily was not a hypertensive disorder, but a vascular disorder (general vasospasm) in pregnancy due to idiopathic etiology. The overall incidence of preeclampsia was 5-14% of all pregnancies. One of the substances responsible for regulating vascular tone is nitric oxide (NO), which produced in endothelial blood vessels. NO and L-citrulline are produced altogether by the reaction between L-arginine and oxygen. L-citrulline levels reflected NO production. This study was aimed to assess the correlation between the L-citrulline level and blood pressure in severe preeclampsia.METHODS: This cross-sectional study was done in Dr. M. Djamil Central General Hospital, Padang, Indonesia The sample size was 36 samples of pregnant women with severe preeclampsia and had yet been given antihypertensive therapy. Sampling was done by consecutive sampling from Obstetrics and Gynecology Division. After maternal examination and measurements L-citrulline levels of cubital venous blood by using enzyme-linked immunosorbent assay (ELISA) method, Pearson correlation was performed to assess the relationship between variables for normally distributed data and Spearman's correlation for abnormal distribution data with significance level p<0.05.RESULTS: Means of L-citrulline levels, systolic blood pressure, diastolic blood pressure, and arterial pressure (MAP) were 87.21 nmol/mL, 179.4 mmHg, 108.3mmHg, and 132.1 mmHg, respectively. Correlation of the L-citrulline level with systolic blood pressure, diastolic blood pressure, and MAP were -0.08, -0.175, and -0.136 (p>0.05), respectively.CONCLUSION: L-citrulline levels had no correlation with blood pressure in severe preeclampsia.KEYWORDS: L-citrulline levels, blood pressure, severe preeclampsia

Plasma citrulline level as a biomarker for cancer therapy-induced small bowel mucosal damage.

Regimen-related mucosal toxicity is extremely common following cytotoxic chemotherapy and radiotherapy. Mucositis is as an important determinant of the inflammatory response and infectious complications in cancer treated patients. Most assessment scales for mucosal damage are focussed on oral mucositis, since it is easy to evaluate. Measuring gastrointestinal musocal damage objectively remains difficult because it cannot be seen directly or readily detected. One of potential non-invasive biomarkers of gastrointestinal mucosal damage is plasma citrulline level. Citrulline is an amino acid produced by small bowel enterocytes. Low concentration of free circulating citrulline signifies severe intestinal mucosal damage in humans with nonmalignant disorders, such as villous atrophy-associated diseases, short bowel syndrome, Crohn's disease, and is used in follow-up after small bowel transplantation. The plasma citrulline level is a reliable and objective biochemical marker of enterocyte mass and function in humans, and therefore can be used to monitor enterocyte toxicity resulting from chemotherapy and radiotherapy during anticancer therapy in patients with severely disturbed gut integrity.

Lactose maldigestion during methotrexate-induced gastrointestinal mucositis in a rat model

Patients with chemotherapy-induced gastrointestinal mucositis suffer from anorexia, diarrhea, and stomach pain, often causing weight loss and malnutrition. When the intestinal function during mucositis would be known, a rational feeding strategy might improve the nutritional state, accelerate recuperation, and increase survival of mucositis patients. We developed a methotrexate (MTX)-induced mucositis rat model to study nutrient digestion and absorption. To determine lactose digestion and absorption of its derivative glucose during mucositis, we injected Wistar rats intravenously with MTX (60 mg/kg) or 0.9% NaCl (controls). Four days later, we orally administered trace amounts of [1-13C]lactose and [U-13C]glucose and quantified the appearance of labeled glucose in the blood for 3 h. Finally, we determined plasma citrulline level and harvested the small intestine to assess histology, myeloperoxidase level, glycohydrolase activity, immunohistochemical protein, and mRNA expression. MTX-treated rats showed profound villus atrophy and epithelial damage. During the experimental period, the absorption of lactose-derived [1-13C]glucose was 4.2-fold decreased in MTX-treated rats compared with controls ( P < 0.01). Lactose-derived [1-13C]glucose absorption correlated strongly with villus length (rho = 0.86, P < 0.001) and with plasma citrulline level (rho = 0.81, P < 0.001). MTX treatment decreased jejunal lactase activity (19.5-fold, P < 0.01) and immunohistochemical protein and mRNA expression (39.7-fold, P < 0.01) compared with controls. Interestingly, MTX treatment did not affect the absorption of [U-13C]glucose during the experimental period. We conclude that lactose digestion is severely decreased during mucositis while glucose absorption is still intact, when supplied in trace amounts. Plasma citrulline level might be a useful objective, noninvasive marker for lactose maldigestion during mucositis in clinic.