Ornithine Research Articles

The correlation between serum total bile acid and alanine aminotransferase of pregnant women and the disorders of neonatal hyperbilirubinemia-related amino acid metabolism

BackgroundTo explore the association between liver metabolism-related indicators in maternal serum and neonatal hyperbilirubinemia (NHB), and further investigate the predictive value of these indicators in NHB-related amino acid metabolism disorders.Methods51 NHB and 182 No-NHB newborns and their mothers who treated in the Fourth Hospital of Shijiazhuang from 2018 to 2022 were participated in the study. The differences in clinical data were compared by the Mann-Whitney U test and Chi-square test. Multivariate logistic regression was used to analyze the relationship between maternal serum indicators and the occurrence of NHB. The correlation analysis and risk factor assessment of maternal serum indicators with NHB-related amino acid metabolic disorders were performed using Spearman correlation analysis and multivariate logistic regression.ResultsCompared to the non NHB group, the NHB group had higher maternal serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALT/AST, and total bile acid (TBA), while lower levels of serum albumin (ALB), total cholesterol (TC) and high-density lipoprotein (HDL). The levels of alanine (ALA), valine (VAL), ornithine (ORN), and proline (PRO) in the newborns were reduced in NHB group, while arginine (ARG) showed a tendency to be elevated. Multiple logistic regression analysis showed that maternal ALT, AST, ALT/AST, and TBA levels were all at higher risk with the development of NHB, whereas ALB, TC, and HDL levels were negatively associated with NHB development. Increasing maternal TBA level was associated with lower ALA (r=-0.167, p = 0.011), VAL (r=-0.214, p = 0.001), ORN (r=-0.196, p = 0.003), and PRO in the newborns (r=-0.131, p = 0.045). Maternal ALT level was negatively associated with ALA (r=-0.135, p = 0.039), VAL (r=-0.177, p = 0.007), ORN (r=-0.257, p < 0.001), while ALT/AST was positively correlated with ARG (r = 0.133, p = 0.013). After adjustment for confounding factors, maternal serum TBA and ALT were the independent risk factor for neonatal ORN metabolic disorders [(adjusted odds ratio (AOR) = 0.379, 95%CI = 0.188–0.762, p = 0.006), (AOR = 0.441, 95%CI = 0.211–0.922, p = 0.030)]. Maternal ALT level was an independent risk factor for neonatal VAL metabolic disorders (AOR = 0.454, 95%CI = 0.218–0.949, p = 0.036).ConclusionsThe levels of high TBA, ALT, AST, and low HDL, TC of maternal were associated with the risk of NHB. Maternal TBA and ALT levels were independent risk factors for NHB-related amino acid disturbances which have value as predictive makers.

Metabolites of L-ARG in Exhaled Breath Condensate and Serum Are Not Biomarkers of Bronchial Asthma in Children.

(1) Background: L-arginine (L-ARG) and its metabolites are involved in some aspects of asthma pathogenesis (airway inflammation, oxidative stress, bronchial responsiveness, collagen deposition). Published data indicate that lungs are a critical organ for the regulation of L-ARG metabolism and that alterations in L-ARG metabolism may be significant for asthma. The aim of this study was to assess the levels of L-ARG and its metabolites in pediatric patients with asthma in serum and exhaled breath condensate (EBC) by mass spectrometric analysis and compare them with non-asthmatic children. (2) Methods: Sixty-five children (37 pediatric patients with bronchial asthma and 28 healthy control subjects) aged 6–17 participated in the study. All participants underwent a clinical visit, lung tests, allergy tests with common aeroallergens, and serum and EBC collection. The levels of biomarkers were determined in both serum and EBC. Analytical chromatography was conducted using an Acquity UPLC system equipped with a cooled autosampler and an Acquity HSS T3 column. Mass spectrometric analysis was conducted using the Xevo G2 QTOF MS with electrospray ionization (ESI) in positive ion mode. (3) Results: Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) levels in serum and EBC did not differ significantly in asthmatic children and healthy control subjects. We found no correlation between forced expiratory volume in one second (FEV1) and L-ARG and its metabolites, as well as between interleukin-4 (IL-4) serum level and L-ARG and its metabolites. Concentrations of ADMA, SDMA, citrulline (CIT), and ornithine (ORN) were higher in serum than EBC in asthmatics and non-asthmatics. By contrast, concentrations of dimethylarginine (DMA) were higher in EBC than serum. ADMA/L-ARG, SDMA/L-ARG, and DMA/L-ARG ratios were significantly higher in EBC than in serum in asthmatics and in non-asthmatics. (4) Conclusions: Serum and EBC concentrations of L-ARG and its metabolites were not an indicator of pediatric bronchial asthma in our study.

Ornithine carbamoyltransferase from psychrophiles to thermophiles: structural evolution of catalytic fold to accommodate physiological diversity.

Here, we have analyzed the enzyme ornithine carbamoyltransferase (OCTase) in different classes of microorganisms belonging to psychrophiles, mesophiles and thermophiles. This OCTase catalyzes the formation of citrulline from carbamoyl phosphate (CP) and ornithine (ORN) in arginine biosynthesis pathway and has certain unique adaptations to regulate metabolic pathways in extreme conditions. The tertiary structure of OCTase showed two binding domains, the CP domain and ORN-binding domain at N and C terminals, respectively. We propose general acid-base catalysis in Pseudomonas gessardii between His259 and Asp220 in which later may act as a recipient of proton in the process. The comparative docking analysis showed that substrate-binding loops have been evolved to accommodate their lifestyles across the physiological temperature range where two substrates bind on two distinct loops in psychrophiles and mesophiles, whereas both the substrates bind on a single-substrate-binding loop in thermophiles and bring down the flexibility of the active site pocket to improve its evolutionary fitness.

Activated whole-body arginine pathway in high-active mice.

Our previous studies suggest that physical activity (PA) levels are potentially regulated by endogenous metabolic mechanisms such as the vasodilatory roles of nitric oxide (NO) production via the precursor arginine (ARG) and ARG-related pathways. We assessed ARG metabolism and its precursors [citrulline (CIT), glutamine (GLN), glutamate (GLU), ornithine (ORN), and phenylalanine (PHE)] by measuring plasma concentration, whole-body production (WBP), de novo ARG and NO production, and clearance rates in previously classified low-active (LA) or high-active (HA) mice. We assessed LA (n = 23) and HA (n = 20) male mice by administering a stable isotope tracer pulse via jugular catheterization. We measured plasma enrichments via liquid chromatography tandem mass spectrometry (LC-MS/MS) and body compostion by echo-MRI. WBP, clearance rates, and de novo ARG and NO were calculated. Compared to LA mice, HA mice had lower plasma concentrations of GLU (71.1%; 36.8 ± 2.9 vs. 17.5 ± 1.7μM; p<0.0001), CIT (21%; 57.3 ± 2.3 vs. 46.4 ± 1.5μM; p = 0.0003), and ORN (40.1%; 55.4 ± 7.3 vs. 36.9 ± 2.6μM; p = 0.0241), but no differences for GLN, PHE, and ARG. However, HA mice had higher estimated NO production ratio (0.64 ± 0.08; p = 0.0197), higher WBP for CIT (21.8%, 8.6 ± 0.2 vs. 10.7 ± 0.3 nmol/g-lbm/min; p<0.0001), ARG (21.4%, 35.0 ± 0.6 vs. 43.4 ± 0.7 nmol/g-lbm/min; p<0.0001), PHE (7.6%, 23.8 ± 0.5 vs. 25.6 ± 0.5 nmol/g-lbm/min; p<0.0100), and lower GLU (78.5%; 9.4 ± 1.1 vs. 4.1 ± 1.6 nmol/g lbm/min; p = 0.0161). We observed no significant differences in WBP for GLN, ORN, PHE, or de novo ARG. We concluded that HA mice have an activated whole-body ARG pathway, which may be associated with regulating PA levels via increased NO production.

Ornithine monooxygenase and RNase J family beta-CASP ribonuclease. Can they be bacteriocins?

Ornithine monooxygenase and RNase J family beta-CASP ribonuclease. Can they be bacteriocins?

Effects of empagliflozin and L-ornithine L-aspartate on behavior, cognitive functions, and physical performance in mice with experimentally induced steatohepatitis

Неалкогольная жировая болезнь печени (НАЖБП) — хроническое заболевание, характеризующееся не только изменениями углеводного и липидного обменов, но и рядом психоневрологических нарушений, включая тревожно-депрессивные расстройства, ухудшение памяти и астенический синдром. Большинство фармакологических исследований направлено на оценку способности препаратов восстанавливать биохимические функции и гистоморфологическую картину печени при НАЖБП; их влияние на течение сопутствующих нарушений изучают редко. Целью работы было оценить влияние эмпаглифлозина и L-орнитина L-аспартата (ОА) на поведение, память и физическую работоспособность мышей линии C57BL/6 при моделировании НАЖБП (6-месячная «западная диета» с еженедельным введением тетрахлорметана). Данная модель вызывает у животных изменение поведения (снижение скорости передвижения на 38 и 35%, p &lt; 0,01; увеличение частоты стоек на 432 и 279%, p &lt; 0,05 и др.), ухудшение долговременной памяти (время поиска в «Лабиринте Барнс» возрастало на 108%, число ошибок — на 439%, p &lt; 0,05), а также снижение физической работоспособности (время вынужденного плавания сократилось на 50%, p &lt; 0,05 и др.). Оба препарата при введении во время диеты снижали тревожность (эмпаглифлозин: число грумингов возросло на 160%, p &lt; 0,05 и на 2173%, p &lt; 0,01; время в белой зоне черно-белой камеры — на 275%, p &lt; 0,05 и др.; ОА: время в открытых рукавах лабиринта увеличилось на 267%, p &lt; 0,05) и способствовали сохранению памяти у мышей с НАЖБП. Особенностью ОА было повышение физической работоспособности животных (время вынужденного плавания увеличилось на 106%, p &lt; 0,05 и др.). Таким образом, эмпаглифлозин и ОА могут положительно влиять на поведенческие и когнитивные функции, а также снижать выраженность астенического синдрома при НАЖБП.

A healthy neonate born at the third pregnancy of a woman with ornithine carbamoyltransferase deficiency under multidisciplinary management

We reported a women with ornithine carbamoyltransferase deficiency who delivered a healthy boy after two pregnancies with adverse outcome with the help of a multidiscipline team. The woman was admitted to Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine with an acute prenatal hyperammonemic episode at 28 gestational weeks of her first pregnancy in 2013 and was diagnosed with ornithine transcarbamylase deficiency. Her hyperammonemic complications were controlled under a well-planned multidisciplinary management including a low-protein diet and appropriate medications assisting nitrogen removal. A boy was delivered by cesarean section at 32 weeks of gestation but died three days later. Mutation analysis revealed a hemizygous c.583G>A (G195R) mutation in the neonatal ornithine carbamyltransferase gene and his mother was a heterozygous carrier with the same mutation. Two years later in 2015, the patient was pregnant spontaneously. However, she received an induced abortion at 21 weeks of gestation because amniocentesis and DNA analysis showed that the male fetus had the same ornithine transcarbamylase gene mutation. The index pregnancy was assisted by in vitro fertilization-embryo transfer and preimplantation genetic diagnosis in 2017 and the woman delivered a healthy boy with the management of a multidisciplinary team. Key words: Ornithine carbamoyltransferase deficiency disease; Gravidity; Peripartum period; Patient care management

Progress and prospects of biomarkers for liver injury in critically ill patients

Liver injury is an independent risk factor for worse prognosis of patients with critically ill.The criteria for diagnosis of liver injury are based on the levels of alanine aminotransferase(ALT ≥ 2 fold the upper limit of normality)or total bilirubin(TBIL≥ 68 μmol/L). All these classic indicators have limitation to early identify liver injury.Recently, accumulated evidences indicated that novel potential biomarkers for predicting liver injury are worth more attention due to quick response to liver injury up to 0.5-2 h. Here, we summarized these potential biomarkers including serum total bile acids, bile acids profiling, regulator of iron metabolism(transferrtin, ferritin and hepcidin), enzymes involved in mitochondria function(GLDH and MDH), key proteins for ornithine circulation pathway(Arg Ⅰ, OCT and ASS), hepatocytes-derived cytokines(CK18, HMGB1 and miR122)and immunologic regulator(MIF). Key words: Liver injury; Biomarker; Critically ill

Not Everything is a Question of Reputation: Safety of Bacteriocinogenic Lab Isolated from Smoked Salmon

Total DNA extracted from bacteriocinogenic and potential probiotic lactic acid bacteria (LAB) (Lactobacillus curvatus ET06, ET30 and ET31, Lactobacillus fermentum ET35, Lactobacillus delbrueckii ET32, Pediococcus acidilactici ET34 and Enterococcus faecium ET05, ET12 and ET88), have been screened for presence of more than 50 genes related to production of biogenic amines (histidine decarboxylase, tyrosine decarboxylase and ornithine decarboxylase), virulence factors (sex pheromones, gelatinase, cytolisin, hyaluronidase, aggregation substance, enterococcal surface protein, endocarditis antigen, adhesion of collagen, integration factors) and antibiotic resistance (vancomycin, tetracycline, erythromycin, gentamicin, chloramphenicol, bacitracin). Tested strains presented low frequencies of presence for virulence genes. Only few genes were detected in some strains, indicating their safety for application in fermented food products. Besides all beneficial properties studied for various LAB, most considered as GRAS, a special attention need to be addressed on the possible presence of virulence factors, production of biogenic amines and antibiotic resistance. Results from appropriate biochemical tests and detected main genes associated to virulence factors and antibiotic resistance in LAB strains, could be considered as potential hazard of application of this organisms in food products. Moreover, additional in vitro and in vivo experiments must be designed in the system simulating GIT conditions in order to investigate deeper the possible expression of the present virulence genes.

Analysis of blood metabolites in preterm infants with bronchopulmonary dysplasia using liquid chromatography-tandem mass spectrometry

Objective To analyze the changes in blood metabolites in premature infants with bronchopulmonary dysplasia (BPD) within 36 h and in the 3rd week after birth in order to find new biomarkers for diagnosis of BPD. Methods The BPD group included 20 premature infants (<32 gestational weeks) hospitalized in the Neonatal Intensive Care Unit (NICU) of the Sixth Affiliated Hospital of Sun Yat-sen University and diagnosed with BPD from January 2014 to October 2016. Another 20 non-BPD premature infants with similar gestational age (within one week) who were admitted during the same period were enrolled in the control group. Blood samples of both groups were collected within 36 h and in the 3rd week after birth. Liquid chromatography-tandem mass spectrometry was used to detect blood metabolites and the obtained data were subjected to metabolomics analysis using orthogonal partial least squares discriminant analysis. Chi-square test (or Fisher's exact test), Mann-Whitney U test or t test was used for statistical analysis. Results (1) Twenty and 11 blood samples were collected within 36 h and in the 3rd week after birth from the BPD and the control group, respectively. Compared with the control group, the interval between premature rupture of membranes and delivery, the average length of hospital stay, non-invasive and invasive mechanical ventilation duration and the total duration of supplemental oxygen during hospitalization in the BPD group were longer [M (P25-P75) or (±s): 13.5 (0.0-98.3) vs 0.0 (0.0-0.0) h, Z=3.049; (66.6±20.5) vs (43.9±9.3) d, t=4.574; 267.0 (199.5-516.1) vs 110.5 (0.0-238.5) h, Z=-3.428; 117.5 (0.0-269.3) vs 0.0 (0.0-72.0) h, Z=-2.785; (1 184.0±386.6) vs (595.9±270.3) h, t=5.576; all P<0.05]. (2) Within 36 h after birth, the levels of glycine, proline, tryptophan and piperamide-C5:1 in the BPD group were decreased obviously compared with those in the control group [(201.59±65.01) vs (290.90±137.56) μmol/L, t=-2.625; 103.55 (72.43-434.57) vs 439.48 (103.80-608.98) μmol/L, Z=-2.245; 29.54 (20.30-41.04) vs 47.42 (29.46-73.57) μmol/L, Z=-2.326; 50.04 (35.29-104.78) vs 95.79 (76.21-129.97) μmol/L, Z=-2.029; all P<0.05]. However, the glutamate level was increased [(224.30±67.40) vs (182.67±40.87) μmol/L, t=2.362, P<0.05]. (3) In the 3rd week after birth, the levels of glycine, proline and tryptophan in the BPD group were lower compared to those in the control group [(185.92±61.51) vs (271.85±115.85) μmol/L, t=-2.177; (39.41±18.22) vs (63.92±17.50) μmol/L, t=-3.217; 90.23 (37.93-146.37) vs 330.15 (47.79-622.90) μmol/L, Z=-2.134; all P<0.05]. However, the ornithine level was higher [(75.09±43.21) vs (39.25±16.53) μmol/L, t=2.569, P<0.05]. Conclusions Glycine, proline and tryptophan in blood are potential biomarkers for early diagnosis of BPD. Key words: Bronchopulmonary dysplasia; Amino acids; Metabolomics; Chromatography, liquid; Tandem mass spectrometry

Influences of gestational diabetes mellitus on neonatal amino acid concentrations

Objective To investigate the influences of maternal gestational diabetes mellitus (GDM) on amino acid levels in neonates. Methods From June 2016 to May 2017, 393 pregnancies diagnosed with GDM in Changzhou Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University and 3 924 normal pregnancies were enrolled in this study. Clinical data of the gravidas and their newborns were collected. Heel blood samples were collected at 72 to 96 hours after birth. Tandem mass spectrometry was performed to detect the levels of 11 amino acids including alanine, arginine, citrulline, glycine, leucine/isoleucine/hydroxyproline, methionine, ornithine, phenylalanine, proline, tyrosine and valine in neonatal heel blood. Differences in amino acid levels between the two groups were compared by t test. Influences of GDM on neonatal amino acid levels were analyzed by multivariate linear regression. Results Compared with the healthy pregnancy group, neonates in the GDM group had higher levels of methionine [(21.01±6.30) vs (19.93±6.47) μmol/L, t=3.159, P=0.002] and phenylalanine [(47.19±9.19) vs (45.78±8.58) μmol/L, t=3.076, P=0.002], but lower levels of alanine [(280.51±64.54) vs (290.15±68.40) μmol/L, t=2.678, P=0.007], proline [(147.64±30.64) vs (152.36±33.57) μmol/L, t=2.680, P=0.007], tyrosine [(85.21±29.50) vs (90.60±33.32) μmol/L, t=3.089, P=0.002] and ornithine [(101.22±28.79) vs (105.83±30.10) μmol/L, t=2.906, P=0.004]. Multivariate linear regression analysis showed that GDM was responsible for the increase of methionine (β=0.69, 95%CI: 0.02 to 1.37, P=0.044) and phenylalanine (β=1.60, 95%CI: 0.69 to 2.51, P=0.001), and the decrease of tyrosine (β=-4.98, 95%CI: -8.42 to -1.54, P=0.005) and ornithine (β=-3.16, 95%CI: -6.30 to -0.02, P=0.048) in neonates. Conclusions GDM neonates has increased of methionine and phenylalanine levels and decreased tyrosine and ornithine levels. Key words: Diabetes, gestational; Infant, newborn; Amino acids; Tandem mass spectrometry

Clinical features of 3 patients from 1 family affected by ornithine transcarbamylase deficiency and gene analysis

目的 探讨鸟氨酸氨甲酰基转移酶缺乏症(OTCD)的临床及遗传特点。 方法 总结郑州大学附属儿童医院收治的1个OTCD家系中两姐弟及其母亲的临床诊疗经过，分析其临床及遗传特点。 结果 先证者，女，2岁2个月起间断呕吐，伴意识障碍，肝功能损伤，血氨增高，血精氨酸降低，尿乳清酸、尿嘧啶增高，疑似OTCD，给予低蛋白饮食、药物及血液透析等治疗，于2岁8个月时死于脑疝。期间先证者母亲再次妊娠，并于产后第4天出现精神异常，于产后15 d死于多器官功能衰竭。产下的男婴于出生第4天死亡。提取先证者死亡后冻存血液中白细胞DNA，基因检测证实鸟氨酸氨甲酰基转移酶(OTC)基因c．275G>A杂合突变。患儿母亲存在相同突变。 结论 OTCD男女均可发病，同一家族成员个体差异显著。对于呕吐、意识障碍、肝功能损伤的患者，均应注意监测血氨水平，及早行基因检测，争取治疗时机，降低病死率。明确致病基因有助于遗传咨询，指导下一胎同胞的产前诊断。

Pathogenicity characteristics of Enterococcus faecium from diseased black bears.

The death of several black bears at the black bear breeding base in Yunnan Pingbian Daweishan is a matter of concern. Multiple black bears exhibited decreased appetite or unusual waste, and some were soporific or suffered from vomiting and anhelation. In order to ascertain the cause of death, 16S rDNA gene sequencing and phylogenetic analysis was performed on bacteria isolated from tissue samples obtained from dead bears. The biochemical characteristics of the isolated bacteria were subsequently analyzed using different biochemical test systems. The bacteria can decompose glucose, but it cannot produce gas. The fermentation study of sucrose, lactose, trehalose, glycerol and mannitol yielded positive results; while it was unable to decompose urea or ODC (ornithine decarboxylase). Basic Local Alignment Search Tool (BLAST) analysis of a ~1500-bp DNA product amplified from the 16S rDNA of the bacterial isolate revealed that Enterococcus faecium from black bears is highly similar to other E. faecium isolates in the National Center for Biotechnology Information (NCBI) database, and the highest sequence similarity (99%) was with the reference strain. In addition, mice infected with the E. faecium isolate succumbed to severe damage to the lungs, liver, spleen, myocardium, and kidney tissues. In summary, the isolated E. faecium from dead black bears induced pathological changes in mice.

Homoarginine and inhibition of human arginase activity: kinetic characterization and biological relevance

The inhibition of arginase, resulting in higher arginine (ARG) availability for nitric oxide synthesis, may account for the putative protective effect of homoarginine (HOMOARG) against atherosclerosis and cardiovascular disease. However, uncertainty exists regarding the significance of HOMOARG-induced arginase inhibition in vivo. A novel UPLC-MS method, measuring the conversion of ARG to ornithine (ORN), was developed to determine arginase 1 and arginase 2 inhibition by HOMOARG, lysine (LYS), proline (PRO), agmatine (AG), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and NG-Monomethyl-L-arginine (L-NMMA). Plasma HOMOARG, ARG and ORN concentrations were further measured in 50 healthy older adults >65 years (27 males and 23 females). HOMOARG inhibited arginase 1 with IC50 and Ki values of 8.14 ± 0.52 mM and 6.1 ± 0.50 mM, and arginase 2 with IC50 and Ki values of 2.52 ± 0.01 mM and 1.73 ± 0.10 mM, respectively. Both arginase isoforms retained 90% activity vs. control when physiological HOMOARG concentrations (1–10 µM) were used. In partial correlation analysis, plasma HOMOARG was not associated with ARG (P = 0.38) or ARG/ORN ratio (P = 0.73) in older adults. Our results suggest that arginase inhibition is unlikely to play a significant role in the reported cardio-protective effects of HOMOARG.

Effects of ornithine aspartate combined with alprostadil in the treatment of severe chronic hepatitis B and its effect on serum tumor necrosis factor-α

Objective To investigate the effect of ornithine aspartate combined with alprostadil in the treatment of severe chronic hepatitis B (CHB), and its effect on serum tumor necrosis factor-α(TNF-α). Methods 80 patients with severe CHB were selected.The patients were divided into the observation group and the control group by digital random method, 40 patients in each group.The control group was given conventional treatment of rest, isoglycyrrhizinate magnesium needle, glutathione needle, plasma, albumin, anti-hepatitis B virus.The observation group received ornithine aspartate combined with alprostadil treatment based on the treatment of the control group.After a continuous treatment of 4 weeks, the curative effect was observed, the changes of liver function before and after treatment was compared.Enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma TNF-α level, and the adverse reactions during treatment were recorded. Results The total effective rate of the observation group was 92.50%, which was significantly higher than 80.00% of the control group (χ2=26.588, P 0.05). After treatment, the TNF-α level of the two groups was significantly decreased, which of the observation group was significantly lower than that of the control group[(176.45±20.41)ng/L vs.(221.43±21.43)ng/L, t=9.613, P 0.05). Conclusion Ornithine aspartate combined with alprostadil in the treatment of severe CHB on the basis of the conventional treatment can apparently enhance clinical effect, improve liver function, decrease plasma TNF-α level and adverse reactions. Key words: Hepatitis B, chronic; Ornithine aspartate; Alprostadil; Tumor necrosis factor alpha

Brain MRI and MR spectroscopy findings of ornithine carbamoyltransferase deficiency in a child: a case report

Brain MRI and MR spectroscopy findings of ornithine carbamoyltransferase deficiency in a child: a case report

Attenuation of Obesity by Ornithine Enriched Blueberry Liquid Starter in 3T3‐L1 Preadipocyte and High‐Fat Diet Fed Obese Mouse Model

The primary objective of this study was to assess ornithine enriched blueberry liquid starter (OB) potential in inhibiting the adipogenesis process in 3T3‐L1 preadipocytes and attenuating obesity related parameters in high‐fat diet induced obese mice. OB did not show any cytotoxic effect, however, treatment with OB resulted in reduction in triglyceride accumulation compared to the blueberry liquid (BB) and non‐treatment control (C). Four‐week‐old C57BL/6J mice were fed with control diets containing 10% kcal from fat (CD) or high‐fat diets containing 60% kcal from fat (HD). Treatment groups were given high fat diet; the samples OB, BB, ornithine (OR) were administrated orally. Compare to the HD control group, the animals given OB showed significant reduction in body weight gain. Furthermore, obesity related parameters like serum lipid profiles were attenuated in the OB treated group. Overall, these results demonstrated the potential of OB in making processed food products which could be capable of attenuating obesity.Support or Funding InformationThis research was financially supported by the Ministry of Trade, Industry, and Energy (MOTIE), Korea, under the “Regional Specialized Industry Development Program” supervised by the Korea Institute for Advancement of Technology (KIAT).

Early onset ornithine transcarbamylase deficiency: two cases report and literatures review

目的 提高对新生儿鸟氨酸氨甲酰基转移酶缺乏症(ornithine carbamoyltransferase deficiency，OTCD)早期临床认识，探讨新生儿期发病的OTCD患儿的治疗并文献复习。 方法 总结2012年至2015年本院收治的2例OTCD患儿的临床资料，分析患儿的临床、生化等特点，利用质谱技术检测患儿血氨基酸和尿有机酸，初步确定诊断。 结果 例1患儿出生第3天起病，首先表现为母乳喂养下吸吮力差，胃纳减，精神偏差，少哭吵，四肢少动作，出生第4天入院，入院后2 h即出现四肢抽搐，反应一般，前囟紧张，颈略有抵抗，入院后14 h予吸氧下出现心率下降，呼吸微弱，瞳孔对光反射消失，皮肤花斑纹，肢端凉，入院后30小时余，呼吸机治疗下，患儿再次出现呼吸、心率下降，病危告知家属，最后放弃治疗。例2患儿生后约10 h出现呕吐，先后呕吐淡黄色黏液及奶汁7次，约25 h出现呼吸困难，48 h出现抽泣样呼吸，呻吟，血氨进行性升高，生后72 h血氨升高至>997.9 μmol/L。入院第5天患儿呼吸机支持下因多脏器功能衰竭死亡。 结论 新生儿期起病的男性OTCD患者预后不佳，起病急、进展快，出生后不久即可出现症状，如未及时抢救，极易死亡。

Plasma free amino acid profile changes in hepatocellular carcinoma patients

Objective The aim of this study was to investigate plasma amino acid profile as a possible diagnostic/prognostic method in patients with hepatocellular carcinoma. Background Many previous reports have shown that metabolism is notably altered in cancer cells. Thus, various methods for cancer diagnosis and prognosis have been developed based on metabolite analysis. Among whole metabolites, amino acids were proposed as suitable candidates for focused metabolomics as they are either ingested or synthesized endogenously and they play an essential physiological role both as basic metabolites and metabolic regulators. Patients and methods This study included 71 hepatocellular carcinoma patients (60 male and 11 female) and 30 chronic hepatitis C virus patients (20 male and 10 female) in addition to 30 healthy controls (25 male and 5 female). Laboratory investigations including complete blood picture, liver function tests, serum α-fetoprotein, hepatitis viral markers (HBsAg and anti-HCVAb) were carried out for all participants. Amino acid assay was carried out using ultra performance liquid chromatography–electrospray ionization-mass spectrometry. Results The study showed a statistically significant increase in methionine, tyrosine, ornithine, citrulline, glycine, phenylalanine, alanine, glutamate, proline, and arginine and a decrease in valine, aspartate, leucine/isoleucine, branched tyrosine ratio (BTR), and Fischer's ratio in hepatocellular carcinoma compared with the control group. Moreover, the study indicated that there was a statistically significant correlation between BTR and platelets, alanine transaminase, albumin, bilirubin, and α-fetoprotein and significant differences in BTR among Child-Pugh A, B, and C. Conclusion Our results suggested that the plasma free amino acid profile is considered valuable for diagnosis and nutritional care in cancer patients. Furthermore, BTR reflects the pathological liver background with a high degree of correlation with other liver functional markers.

Metabolomic profile in biliary atresia compared with cholestasis in pediatric patients: a comparative study

Objectives To compare different levels of amino acid and acyl carnitine profiles to give an insight about metabolic pathways in cholestasis and biliary atresia (BA) in pediatric patients compared with controls. Background Early detection is the most effective way to improve the clinical outcome of BA. Emerging metabolomics such as amino acid and acyl carnitine provide a powerful platform for discovering new biomarkers and biochemical pathways to improve early diagnosis. Participants and methods This study includes 35 BA patients, 35 patients with neonatal cholestasis (NC) rather than BA, and 35 healthy controls. Liver function tests, abdominal ultrasound, and liver biopsy were performed on all participants. The amino acid and acyl carnitine profile using high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) was performed. Results Data revealed a statistically significant increase in methionine, glutamate, and citrulline (P < 0.001, P < 0.001 and P = 0.02, and P < 0.001, respectively) and a decrease in the branched-chain amino acid and fisher ratio (P = 0.02 and 0.001 and P = 0.001, respectively) in both the studied patient groups compared with the control group; there was also an increase in ornithine (P = 0.04) and a decrease in glycine (P = 0.04) amino acid in the BA group compared with the control group and an increase in arginine (P = 0.004) and aromatic amino acids (P = 0.001) and a decrease in the simplified fisher ratio (P < 0.001) in the non-BA group compared with the control group. Results also indicated a statistically significant increase in both patient groups compared with the control group regarding free carnitine (P < 0.001) and almost all studied acyl carnitines, whereas there was a significant decrease in the fisher ratio (P = 0.005) and the simplified fisher ratio (P = 0.004) and a significant increase in butyryl carnitine (C4) (P = 0.004) and octadecanoyl carnitine (C18) (P = 0.006) in the non-BA group compared with the BA group. Conclusion There is a common metabolic pathway for both BA and other causes of NC; however, there is a metabolic profile shift of amino acid and acyl carnitine in BA from other causes of NC detected by LC-MS/MS. This metabolic shift can be potentially developed into a useful diagnostic tool and can contribute towards understanding the disease mechanism.