Citrulline Levels Research Articles

Untargeted Metabolomics Sensitively Differentiates Gut Bacterial Species in Single Culture and Co-Culture Systems.

Gut microbiome plays a vital role in human health, and its characteristic has been widely identified through next-generation sequencing techniques. Although with great genomic insights into gut microbiome, its functional information is not clearly elaborated through metagenomic techniques. On the other hand, it is suggested that fecal metabolome can be used as a functional readout of the microbiome composition; therefore, we designed a proof-of-concept study to first characterize the metabolome of different gut microbes and then investigate the relationship between bacterial metabolomes and their compositions in co-culture systems. We selected eight representative bacteria species from Bifidobacterium (2), Bacteroides (1), Lactobacillus (4), and Akkermansia (1) genera as our model microbes. Liquid chromatography coupled mass spectrometry-based untargeted metabolomics was utilized to explore the microbial metabolome of bacteria single cultures and co-culture systems. Through spectral comparisons, our results showed that untargeted metabolomics could capture the similarity and differences in metabolic profiles from eight representative gut bacteria. Also, untargeted metabolomics could sensitively differentiate gut bacterial species based on our statistical analyses. For example, citrulline and histamine levels were significantly different among four Lactobacillus species. In addition, in the co-culture systems with different bacteria population ratios, gut bacterial metabolomes can be used to quantitatively reflect bacterial population in a mixed culture. For instance, the relative abundance of 2-hydroxybutyric acid changed proportionately with the changed population ratio of Lactobacillus reuteri in the co-culture system. In summary, we proposed a workflow that could demonstrate the capability of untargeted metabolomics in differentiating gut bacterial species and detecting their characteristic metabolites proportionally to the microbial population in co-culture systems.

Protective Effect of Intestinal Blautia Against Neutropenic Fever in Allogeneic Transplant Recipients.

Neutropenic fever (NF) occurs in >70% of hematopoietic cell transplant (HCT) recipients, without a documented cause in most cases. Antibiotics used to prevent and treat NF disrupt the gut microbiota; these disruptions predict a higher posttransplantation mortality rate. We hypothesized that specific features in the gut microbial community may mediate the risk of NF. We searched a large gut microbiota database in allogeneic HCT recipients (12 546 stool samples; 1278 patients) to find pairs with NF (cases) versus without NF (controls) on the same day relative to transplantation and with a stool sample on the previous day. A total of 179 such pairs were matched as to the underlying disease and graft source. Several other important clinical variables were similar between the groups. The gut microbiota of cases on the day before NF occurrence had a lower abundance of Blautia than their matched controls on the same day after transplantation, suggesting a protective role for Blautia. Microbiota network analysis did not find any differences in community structure between the groups, suggesting a single-taxon effect. To identify putative mechanisms, we searched a gut microbiome and serum metabolome database of patients with acute leukemia receiving chemotherapy and identified 139 serum samples collected within 24 hours after a stool sample from the same patient. Greater Blautia abundances predicted higher levels of next-day citrulline, a biomarker of total enterocyte mass. These findings support a model in which Blautia protects against NF by improving intestinal health. Therapeutic restoration of Blautia may help prevent NF, thus reducing antibiotic exposures and transplantation-related deaths.

The diagnostic challenge of mild citrulline elevation at newborn screening.

Citrulline is a target analyte measured at expanded newborn screening (NBS) and its elevation represents a biomarker for distal urea cycle disorders and citrin deficiency. Altered ratios of citrulline with other urea cycle-related amino acids are helpful for the differential diagnosis. However, the use of cut-off values in screening programmes has raised the issue about the interpretation of mild elevation of citrulline levels detected at NBS, below the usual range observed in the "classical/severe" forms of distal urea cycle disorders and in citrin deficiency. Herein, we report ten subjects with positive NBS for a mild elevation of citrulline (<100 μmol/L), in whom molecular investigations revealed carriers status for argininosuccinate synthase deficiency, a milder form of argininosuccinate lyase deficiency and two other diseases, lysinuric protein intolerance and dihydrolipoamide dehydrogenase deficiency, not primarily affecting the urea cycle. To guide the diagnostic process, we have designed an algorithm for mild citrulline elevation (<100 μmol/L) at NBS, which expands the list of disorders to be included in the differential diagnosis.

Corticosteroid suppresses urea-cycle-related gene expressions in ornithine transcarbamylase deficiency

BackgroundOrnithine transcarbamylase deficiency (OTCD) is most common among urea cycle disorders (UCDs), defined by defects in enzymes associated with ureagenesis. Corticosteroid administration to UCD patients, including OTCD patients, is suggested to be avoided, as it may induce life-threatening hyperammonemia. The mechanism has been considered nitrogen overload due to the catabolic effect of corticosteroids; however, the pathophysiological process is unclear.MethodsTo elucidate the mechanism of hyperammonemia induced by corticosteroid administration in OTCD patients, we analyzed a mouse model by administering corticosteroids to OTCspf−ash mice deficient in the OTC gene. Dexamethasone (DEX; 20 mg/kg) was administered to the OTCspf−ash and wild-type (WT) mice at 0 and 24 h, and the serum ammonia concentrations, the levels of the hepatic metabolites, and the gene expressions related with ammonia metabolism in the livers and muscles were analyzed.ResultsThe ammonia levels in Otcspf−ash mice that were administered DEX tended to increase at 24 h and increased significantly at 48 h. The metabolomic analysis showed that the levels of citrulline, arginine, and ornithine did not differ significantly between Otcspf−ash mice that were administered DEX and normal saline; however, the level of aspartate was increased drastically in Otcspf−ash mice owing to DEX administration (P < 0.01). Among the enzymes associated with the urea cycle, mRNA expressions of carbamoyl-phosphate synthase 1, ornithine transcarbamylase, arginosuccinate synthase 1, and arginosuccinate lyase in the livers were significantly downregulated by DEX administration in both the Otcspf−ash and WT mice (P < 0.01). Among the enzymes associated with catabolism, mRNA expression of Muscle RING-finger protein-1 in the muscles was significantly upregulated in the muscles of WT mice by DEX administration (P < 0.05).ConclusionsWe elucidated that corticosteroid administration induced hyperammonemia in Otcspf−ash mice by not only muscle catabolism but also suppressing urea-cycle-related gene expressions. Since the urea cycle intermediate amino acids, such as arginine, might not be effective because of the suppressed expression of urea-cycle-related genes by corticosteroid administration, we should consider an early intervention by renal replacement therapy in cases of UCD patients induced by corticosteroids to avoid brain injuries or fatal outcomes.

Relationship of citrulline and tissue transglutaminase antibody with duodenal histopathology among children with celiac disease

ObjectivesNon-invasive biomarkers, for the diagnosis of celiac disease, can reduce the need for biopsy, particularly in pediatric patients. The aim of this study was to investigate the levels tissue transglutaminase antibody (tTG) and plasma citrulline and its correlation with intestinal biopsy. MethodsIn this cross-sectional descriptive study, Pediatric patients with celiac disease referred to (XXX)were included. The patients underwent tTG antibody test along with plasma citrulline measurements using HPLC ((high performance liquid chromatography). Biopsy was performed in all the patients and clinical and demographic findings were recorded in a patient form. The data were statistically analyzed using SPSSv22. ResultsOf 118 patients with celiac disease, the mean level of citrulline in patients was 17.48 ± 6.92 and the mean tTG titer was 183.17 ± 41.25. The two variables were inversely correlated with each other, p < 0.01. With an increase in Marsh levels, a significant reduction in citrulline levels and an increase in plasma tTG levels were seen, p < 0.01, respectively. The mean citrulline and tTG titer was not associated with gender and the age of the patients. ConclusionOur findings indicate that citrulline and tTG antibody titer are significant biomarkers for the diagnosis of celiac disease and the severity of intestinal atrophy among pediatric patients.

Posaconazole bioavailability of the solid oral tablet is reduced during severe intestinal mucositis

ObjectivesThis study aimed to describe the absolute oral bioavailability of the solid oral formulation of posaconazole and the impact of severe intestinal mucositis in haematology patients. This study also aimed to describe posaconazole protein binding in haematology patients. MethodsA pharmacokinetic study was performed of patients receiving induction chemotherapy or a haematopoietic cell transplantation who were randomized to receive 7 days of intravenous posaconazole therapy followed by 9 days of oral therapy, or vice versa. Patients received a posaconazole licensed dose until day 12, after which a reduced once-daily dose of 200 mg was given. At days 7, 12, and 16, blood samples were obtained for pharmacokinetic curves, and trough samples were collected on all other days. Total and unbound posaconazole pharmacokinetics were analyzed by population pharmacokinetic modelling. The presence of severe intestinal mucositis was assessed by plasma citrulline levels and analyzed as a binary covariate using 10 μmol/L as the cut-off. Monte Carlo simulations were performed to simulate posaconazole exposure at a steady state. ResultsTwenty-three patients were included for analysis, with 581 total posaconazole concentrations and 91 paired unbound concentrations. Absolute bioavailability in the final model was estimated at 51.4% (percentage relative standard error (%RSE): 56.5) and 67.6% (%RSE: 75.0) in patients with and without severe intestinal mucositis, respectively. Posaconazole unbound fraction was estimated at 2.7% (%RSE: 3.9). DiscussionPosaconazole bioavailability is reduced in haematological patients with severe intestinal mucositis, requiring an increase in oral posaconazole dose to 400 mg twice daily on day 1, followed by 400 mg once daily or a switch to intravenous therapy.

Investigating myelin oligodendrocyte glycoprotein antibodies in hereditary citrullinemia

Metabolites like lipids, amino acids or peptides can affect the immune system. Citrulline is an amino acid that activates several inflammatory pathways. Serum citrulline levels are markedly elevated in hereditary citrullinemia type 1 (CTLN1), and cases with CTLN1 have have been described with inflammatory lesions of the central nervous system (CNS). This suggests the presence of a relatively proinflammatory state in CTLN1. We therefore tested sera of CTLN1 patients for anti-myelin oligodendrocyte glycoprotein (MOG) antibodies which are a frequent cause of inflammatory CNS disorders in young patients. Patients with CTLN1 (n = 15) and control groups consisting of phenylketonuria (n = 22), juvenile idiopathic arthritis (n = 13), pediatric onset systemic lupus erythematosus (n = 17) and healthy controls (n = 48) were tested for serum anti-MOG IgG and anti-MOG IgG1 antibodies in a live-cell based assay. Serum citrulline levels were elevated in 14/15 CTLN1 patients at the time of the study. No clear anti-MOG IgG positivity was detected in any of the CTLN1 or control groups. One CTLN1 and one healthy control case with anti-MOG IgG titers close to borderline were also tested for MOG-specific IgG1, with similar results. These findings did not support the role of elevated serum citrulline levels in facilitating antibody response against MOG. Other pathways that can be investigated in CTLN1 include lymphocytic responses against neural antigens or any direct effects of citrulline on neural tissue.

THE EFFECT OF S-ADEMETIONINE ON PLASMA CITRULLINE LEVEL DURING CHEMOTHERAPY-INDUCED OXIDATIVE STRESS IN PATIENTS WITH CHRONIC LYMPHOPROLIFERATIVE DISORDERS.

The aim: To investigate the effect of S-ademetionine on plasma citrulline level in patients with chronic lymphoproliferative disorders (CLPD) during chemotherapy-induced oxidative stress. Materials and methods: 25 patients with CLPD were examined. Examinations were conducted twice: before chemotherapy (CT) and after 3 courses of CT. Several biochemical markers in the blood were determined: the activity of catalase, the level of plasma citrulline, the concentration of N-acetylneuraminic acid (NANA) and the concentration of substances that form a trimethine complex (TBARS) with 2-thiobarbituric acid. Patients were divided into groups: І (n=14) - patients who underwent only CT; ІІ (n=16) - patients who during CT received S-ademetionine, at a dose of 1000 mg/day intravenously for 10 days, then 500 mg twice a day for 20 days. ІІІ (n=20) -the control group of 20 practically healthy individuals. Results: Patients in both groups with CLPD had pre-existed mucosal injury that was characterized by 1.25 (p=0.0025) and 1.26 times (р=0.006) higher blood NANA concentration compared to the control group. The conduction of CT was associated with enterocytes dysfunction, which was characterized by 1,66 times (p=0,0002) lower plasma citrulline level in patients of group I compared to the initial examination. The infusion of S-ademetionine attenuated intestinal dysfunction that was associated with 1,23 times (p=0,0005) higher blood citrulline level after the CT as compared to group I. Conclusions: The infusion of S-ademetionine as adjuvant treatment in patients with CLPD provided effective prophylaxis of intestinal injury that was associated with higher blood citrulline level after the conduction of CT.

Usefulness of serum BUN or BUN/creatinine ratio as markers for citrin deficiency in positive cases of newborn screening

Citrin deficiency belongs to a group of urea cycle disorders that can be identified during newborn screening by measuring citrulline, phenylalanine, methionine, and galactose levels. Early diagnosis of citrin deficiency is beneficial as disease-specific interventions such as permission of food preference and/or supplementation of medium-chain triglyceride can prevent metabolic decompensation. However, there are currently no laboratory tests for the diagnosis of citrin deficiency in routine clinical practice. Our retrospective study investigated the diagnostic characteristics of citrin deficiency during infancy at secondary newborn screening. The present study included 10 patients with citrin deficiency and 35 controls without the condition. The positive likelihood ratios for serum levels of blood urea nitrogen (BUN) levels were 6.8 at the first visit, 3.2 at age ≤ 60 days, and 17.5 at age ≤ 100 days. The serum BUN/creatinine ratio also showed a high positive likelihood ratio (3.9 at first visit, 16.0 at age ≤ 60 days, and 24.5 at age ≤ 100 days). Therefore, the serum BUN or BUN/creatinine ratio may help to identify patients with citrin deficiency during newborn screening. Further studies are required to confirm its diagnostic accuracy in a larger cohort and elucidate the underlying mechanisms involved.

Citrulline Accumulation Mechanism of Pediococcus acidilactici and Weissella confusa in Soy Sauce and the Effects of Phenolic Compound on Citrulline Accumulation.

Citrulline is one of the major precursors of ethyl carbamate in soy sauce, and the accumulation of citrulline is attributed to the metabolism of arginine by bacteria with the arginine deiminase (ADI) pathway. However, key strains and factors affecting citrulline accumulation are not yet clear. In this study, two key strains of Pediococcus acidilactici and Weissella confusa were isolated from soy sauce moromi, and the regularity of citrulline formation was studied. Results showed that the conversion rates from arginine to citrulline (A/C rate) and the citrulline accumulation ability of W. confusa and P. acidilactici significantly increased in the presence of different concentrations of NaCl, indicating that salt stress was the main factor for citrulline accumulation. The inconsistent expression of arc genes by salt stress was the reason for citrulline accumulation for P. acidilactici, but for W. confusa, it may be due to the influence of arginine/citrulline on the transportation system: the intracellular citrulline could neither transport to extracellular space nor convert into ornithine. Environmental factors greatly influenced citrulline accumulation of the two key bacteria; A/C rate and citrulline formation in both strains decreased at low temperature (15°C) under high salt stress, but opposite effects were observed for the two key strains under anaerobic light condition. Moreover, quercetin and gallic acid significantly decreased the A/C rate and citrulline accumulation ability of the two key strains. The optimal quercetin and gallic acid as suggested by simulation experiment were 100 and 10 mg/l, respectively, and the lowest A/C rate of 28.4% and citrulline level of 1326.7 mg/l were achieved in the simulation system. This study explored the main factors for citrulline formation by the two key strains and proposed a targeted way to control citrulline in soy sauce.

Apob-48 levels are related to parenteral nutrition dependence in patients with short bowel syndrome: a potential biomarker of intestinal failure

Rationale: Short bowel syndrome with intestinal failure (SBS–IF) is a rare condition that requires parenteral nutrition (PN). Citrulline levels are correlated with small bowel length in SBS-IF patients but evidence varies according to clinical settings. Apolipoprotein B-48 (apoB-48) is a protein exclusively synthetized by enterocytes. The secretion is associated with the chylomicron during the postprandial phase. We hypothesized that circulating apoB-48 levels could be a better reflect of the absorptive function of the remnant gut in patients with SBS-IF.

Understanding early Alzheimer's disease pathology by combining neurochemicals with EEG

The association between neurochemical pathways and Electroencephalogram (EEG) signals has not been fully explored. We previously showed alpha desynchronization during interference testing decreased in preclinical Alzheimer's disease. We aim to explore how neurochemical dysfunction corresponds to alpha desynchronization.Elderly participants were classified clinically as cognitively healthy (CH, n=14) using the Uniform Data System-3. Cerebrospinal fluid amyloid ß42 and tau levels were measured by immunoassays, and CH was subdivided into participants with normal Ab42 /tau (CH-NAT, n=6) or pathological Ab42 /tau (CH-PAT, n=8). Plasma neurotransmitters and amino levels were measured using a LC/MS method. EEG was recorded during Stroop interference testing for alpha desynchronization (reflect brain activities), where participants were asked to respond to each colored word for the color of the ink, when color and word matches (congruent) or does not match (incongruent). We compared the relationships of alpha desynchronization at brain regions (frontal-F, central-C, parietal-P, left temporal-LT, right temporal-RT, occipital-O) and neurochemicals between the two groups.Plasma diaminobutyric acid (DABA) levels negatively correlated with alpha desynchronization in CH-NAT (FCP: r=-0.98∼-0.88, p=0.005∼0.049) but not in CH-PATs. Similarly, plasma melatonin negatively correlated with alpha desynchronization during congruent trials in CH-NAT (P: r=-1, p=0.003) but not in CH-PATs. For incongruent trials, citrulline levels positively correlated with EEG recordings in CH-NATs (C,LT: r=0.86∼0.92, p=0.013∼0.003), while an opposite trend was observed in CH-PATs (r=-0.69∼-0.78, p=0.057∼0.022). Glutamine and histidine negatively correlated with alpha desynchronization during incongruent recordings in the CH-NAT but not in CH-PAT state. Plasma adrenaline positively correlated with alpha desynchronization during incongruent recordings in the CH-NAT (C,LT) but not in CH-PATs. Homocysteine levels negatively correlated with alpha power in CH-PATs (F,C,P,RT: r=-0.84∼-0.74, p=0.010∼0.034), but not in CH-NATs.Our exploratory studies show different association of plasma neurochemical levels with alpha desynchronization. The most significant changes for our small sample size were observed for neurotransmitter metabolites (DABA, glutamine, adrenaline) and antioxidants (homocysteine). Validation of these data using a larger sample size is ongoing. These studies will provide a rationale for modulating neurochemical plasma levels to prevent early AD cognitive deficits and motivate EEG use to monitor the efficacy of these early interventions.

Development of a self-limiting model of methotrexate-induced mucositis reinforces butyrate as a potential therapy

Gastrointestinal mucositis is a complication of anticancer treatment, with few validated in vitro systems suitable to study the complex mechanisms of mucosal injury. Therefore, we aimed to develop and characterize a chemotherapeutic-induced model of mucositis using 3D intestinal organoids. Organoids derived from mouse ileum were grown for 7 days and incubated with different concentrations of the chemotherapeutic agent methotrexate (MTX). Metabolic activity, citrulline levels and cytokine/chemokine production were measured to determine the optimal dosage and incubation time. The protective effects of folinic acid on the toxicity of MTX were investigated by pre-treating organoids with (0.0005–50 µg/mL) folinic acid. The impact of microbial-derived short-chain fatty acids was evaluated by supplementation with butyrate in the organoid model. MTX caused a dose-dependent reduction in cell metabolic activity and citrulline production that was salvaged by folinic acid treatment. Overall, MTX causes significant organoid damage, which can be reversed upon removal of MTX. The protective effect of folinic acid suggest that the organoids respond in a clinical relevant manner. By using the model for intervention, it was found that prophylactic treatment with butyrate might be a valuable strategy for prophylactic mucositis prevention.

A Case of Pyruvate Carboxylase Deficiency With Longer Survival and Normal Laboratory Findings

Pyruvate carboxylase deficiency (PCD) is a rare autosomal recessive defect in a biotin-containing enzyme, Pyruvate carboxylase, which is considered as an enzyme of TCA-cycle regulation, gluconeogenesis, lipogenesis, and biosynthesis of neurotransmitters. Increased lactate to pyruvate ratio and decreased three hydroxybutyrates to acetoacetate are the main biochemical features of PCD. The elevated level of Citrulline, Proline, and Lysine with a short life span has been reported previously. Patients’ survival in almost all cases is below three months. Here, the authors aimed to report a girl with manifestations of Type B of PCD and longer survival (two-year and four-month-old). This patient did not have any changes in amino acid level, which was a unique case of Type B of PCD.

Serum Amino Acid Levels and Mortality in Patients Undergoing Percutaneous Endoscopic Gastrostomy.

To evaluate the effect of feeding via percutaneous endoscopic gastrostomy tube (PEG) on serum amino acid levels and mortality. Descriptive study. University of Health Sciences, Umraniye Training and Research Hospital, Istanbul, Turkey, from January 2016 to February 2019. Patients over 18 years of age, who were indicated for PEG due to loss of swallowing reflex, were included in the study. The follow-up period of the study was one year. The patients were reevaluated on the 3rd, 6th, and 12th months after inclusion. Anthropometric measurements, and nutritional status were evaluated at each visit, and quantitative amino acid levels were analysed. Statistical significance was accepted as p <0.05. The study was carried out with a total of 53 cases (23 men and 30 women) ranging in the age from 18 to 91 years. While 13 patients were still alive, 40 patients died before completing one year. The levels of glutamine, leucine, taurine, and threonine were significantly different between surviving patients and dead. A statistically significant difference was found between the levels of citrulline (p <0.001), ornithine (p = 0.036) and tyrosine (p = 0.011) during the four different visits of patients who survived. In patients who died, a significant difference was found between the levels of threonine, ornithine, and aspartic acid (p <0.043 for all) between visits. Citrulline and tyrosine levels were found to be significantly increased in surviving patients. The amino acid profiles of malnourished patients vary considerably. Increase in citrulline, ornithine and tyrosine levels are noted in surviving patients. Key Words: Amino acid, Percutaneous endoscopic gastrostomy, Malnutrition, Mortality.

Study of arginine metabolism in medication overuse chronic migraine: possible defect in NO synthesis

The pathogenesis of the pain that occurs in episodic migraine attack is due to the activation of the trigeminal system's first neuron receptors located on vessel wall. The release from the endothelium of nitric oxide, a product of arginine metabolism, causes vasodilation and stretching of the vascular trigeminal system and promotes pain. It is unknown whether this same metabolic event is involved in the pain accompanying chronic migraine. To understand the possible role of arginine in the pathogenesis of chronic migraine patients, we evaluated the metabolism of arginine in plasma of chronic migraine and control subjects. We evaluated the metabolism of arginine in a group of patients affected by chronic migraine. Quantification of arginine, ornithine, citrulline, monomethyl arginine (NMMA), dimethylarginines (ADMA, SDMA), and tyramine was performed by ultra-performance liquid chromatography coupled with a triple quadrupole mass spectrometer. Chronic migraine patients showed low plasma levels of arginine, significantly elevated levels of ornithine, ADMA, and NMMA whereas the levels of citrulline and SDMA were in the range of controls. The elevated levels of ADMA and NMMA, inhibitors of nitric oxide synthase, suggest that the metabolism of arginine may be inhibited with a possible reduction of NO release in the circulation of chronic patients. This suggests that the origin of pain may not be related to the vasodilation of trigeminal vascular system that occurs in episodic migraine patients.

Arginine metabolism and nitric oxide turnover in the ZSF1 animal model for heart failure with preserved ejection fraction

Endothelial dysfunction and altered nitric oxide (NO) metabolism are considered causal factors in heart failure with preserved ejection fraction (HFpEF). NO synthase activity depends on the availability of arginine and its derivatives. Thus, we analyzed arginine, associated metabolites, arginine-metabolizing enzymes and NO turnover in 20-week-old female healthy lean (L-ZSF1) and obese ZSF1 rats (O-ZSF1) with HFpEF. Serum, urine and lysates of liver, kidney and heart were analyzed. There were significantly lower lysine (− 28%), arginine (− 31%), homoarginine (− 72%) and nitrite (− 32%) levels in serum of O-ZSF1 rats. Ornithine (+ 60%) and citrulline (+ 20%) levels were higher. Similar results were found in the heart. Expression of arginine consuming enzymes in liver and kidney was unchanged. Instead, we observed a 5.8-fold higher arginase 1 expression, presumably of granulocyte origin, in serum and > fourfold increased cardiac macrophage invasion in O-ZSF1. We conclude that inflammatory cells in blood and heart consume arginine and probably homoarginine via arginase 1 and inducible NO synthase and release ornithine and citrulline. In combination with evidence for decreased NO turnover in O-ZSF1 rats, we assume lower arginine bioavailability to endothelial NO synthase.

Adipokine, gut and thyroid hormone responses to probiotic application in chukar partridges (Alectoris chukar) exposed to heat stress.

The aim of this study was to investigate the effect of Lactobacillus reuteri E81 (LRE) probiotic supplementation on heat stress responses in chukar partridges (Alectoris chukar). The birds were divided into two groups, one of which was exposed to heat stress (HS). Within each group, four subgroups, each including 64 birds, were created for the three treatment doses (200, 400 or 600 mg/kg) of LRE and the control. The experiment was started with day-old birds, kept at a temperature of 25 °C or 37 °C. After a 7-day adjustment period, the LRE supplementation lasted for 35 days. The levels of different adipokines, including visfatin (VF), adiponectin (ADP), chemerin (CHEM), as well as the concentration of plasma citrulline (CIT) and the levels of thyroid hormones (T3 and T4) and thyroid-stimulating hormone (TSH) in the blood were measured at 21 and 42 days of age. A significant correlation (P < 0.01) was found between LRE supplementation and the decrease in serum VF, ADP, CIT, T3 and T4 levels in partridges exposed to HS. On the other hand, no significant relationship was found between LRE supplementation and the serum CHEM and TSH levels (P > 0.05). We concluded that the addition of 600 mg/kg LRE is beneficial in preventing intestinal damage and inflammation provoked by HS.

Plasma Citrulline Level In Preterm Neonates With Necrotizing Enterocolitis

Abstract 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 &amp;lt;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 &amp;lt; 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.

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

Abstract 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.