Acceptability of plasma ammonia results when samples are not transported and processed under ideal conditions.

BACKGROUND: It is recommended that samples for plasma ammonia analysis are kept chilled and processed promptly as in vitro metabolism causes falsely elevated results. Rejection of unsuitable samples can cause delayed diagnosis and treatment of hyperammonaemia with potentially serious clinical consequences. The Metabolic Biochemistry Network (MetBioNet) hyperammonaemia guideline recommends analysis of samples not collected under ideal conditions and reporting with appropriate comments. An audit found that some laboratories did not follow this guidance. An investigation was performed into whether storage at controlled room temperature and delayed sample processing affected interpretation of plasma ammonia results. METHODS: Eleven healthy volunteers provided informed consent. Blood was taken from each into 14 paediatric EDTA blood sample tubes, one placed immediately on ice, the others in a rack at room temperature. The chilled and baseline room temperature samples were centrifuged and plasma analysed by the Roche Ammonia (NH3L2) method. Samples stored at room temperature were analysed at 10-min intervals up to 2 h. RESULTS: Baseline room temperature ammonia was higher than in the chilled sample (19 ± 6.6 µmol/L [mean ± standard deviation] and 18 ± 6.6 µmol/L, respectively). Ammonia increased further by 0.09 ± 0.02 µmol/L per minute to 30 ± 8.4 µmol/L at 2 h. No result was above the reference range (50 µmol/L). No healthy subject with normal baseline ammonia would have been erroneously identified as having hyperammonaemia. CONCLUSIONS: Results support MetBioNet guidance that laboratories accept blood samples for ammonia analysis which are not processed under ideal conditions.

Brain Gray Matter Alterations in Hepatic Encephalopathy: A Voxel-Based Meta-Analysis of Whole-Brain Studies.

Background: Previous studies on voxel-based morphometry (VBM) have found that there were gray matter alterations in patients with hepatic encephalopathy (HE). However, the reported results were inconsistent and lack a quantitative review. Therefore, this study aims for a quantitative meta-analysis of VBM analysis on patients with HE. Methods: The studies in our meta-analysis were collected from Pubmed, Web of Science, and Embase, which were published from January 1947 to October 2021. The seed-based d mapping (SDM) method was applied to quantitatively estimate the regional gray matter abnormalities in patients with HE. A meta-regression analysis was applied to evaluate the relationship between plasma ammonia and gray matter alteration. Results: There were nine studies, with sixteen datasets consisting of 333 participants with HE and 429 healthy controls. The pooled and subgroup meta-analyses showed an increase in gray matter volume (GMV) in the bilateral thalamus and the calcarine fissure but a decrease in the GMV in the bilateral insula, the basal ganglia, the anterior cingulate gyrus, and the cerebellum. The meta-regression showed that plasma ammonia was positively associated with the GMV in the left thalamus but was negatively associated with the GMV in the cerebellum and the bilateral striatum. Conclusion: Gray matter volume in patients with HE largely varied and could be affected by plasma ammonia. The findings of this study could help us to better understand the pathophysiology of cognitive dysfunction in patients with HE.

Ventilatory sensitivity to ammonia in the Pacific hagfish (Eptatretus stoutii), a representative of the oldest extant connection to the ancestral vertebrates.

Ventilatory sensitivity to ammonia occurs in teleosts, elasmobranchs and mammals. Here, we investigated whether the response is also present in hagfish. Ventilatory parameters (nostril flow, pressure amplitude, velar frequency and ventilatory index, the last representing the product of pressure amplitude and frequency), together with blood and water chemistry, were measured in hagfish exposed to either high environmental ammonia (HEA) in the external sea water or internal ammonia loading by intra-vascular injection. HEA exposure (10 mmol l-1 NH4HCO3 or 10 mmol l-1 NH4Cl) caused a persistent hyperventilation by 3 h, but further detailed analysis of the NH4HCO3 response showed that initially (within 5 min) there was a marked decrease in ventilation (80% reduction in ventilatory index and nostril flow), followed by a later 3-fold increase, by which time plasma total ammonia concentration had increased 11-fold. Thus, hyperventilation in HEA appeared to be an indirect response to internal ammonia elevation, rather than a direct response to external ammonia. HEA-mediated increases in oxygen consumption also occurred. Responses to NH4HCO3 were greater than those to NH4Cl, reflecting greater increases over time in water pH and PNH3  in the former. Hagfish also exhibited hyperventilation in response to direct injection of isotonic NH4HCO3 or NH4Cl solutions into the caudal sinus. In all cases where hyperventilation occurred, plasma total ammonia and PNH3  levels increased significantly, while blood acid-base status remained unchanged, indicating specific responses to internal ammonia elevation. The sensitivity of breathing to ammonia arose very early in vertebrate evolution.

Brain MRI findings in acute hepatic encephalopathy in liver transplant recipients.

Acute hepatic encephalopathy has significant morbidity and mortality in liver transplant recipients unless it is promptly treated. We evaluated the brain magnetic resonance (MR) imaging findings associated with acute hepatic encephalopathy in transplant recipients. We retrospectively reviewed the clinical and imaging data and outcomes of twenty-five liver transplant patients (16 male; mean age, 49.3 years) with clinically diagnosed acute hepatic encephalopathy and forty liver transplant patients (20 males; mean age, 45.5 years) without neurological symptoms suggestive of hepatic encephalopathy at our institution. Bilateral symmetric hyperintensities of the insular cortex and cingulate gyrus were observed in twenty-one patients (84.00%), bilateral symmetric extensive increased cortical signal intensity (involving two or more regions) was observed in 72.00% of the patients, leptomeningeal enhancement in 73.68%, and visualization of prominent venules in 52.00%. The most common symptom at diagnosis was rigidity (n = 14), and the plasma ammonia levels ranged from 68.63 to 192.16 µmol/L. After active treatment, 17 patients gradually recovered, four patients suffered from mild or moderate neurologic deficits, and four patients with widespread brain edema died. The specific brain MR imaging features were bilateral symmetric increased cortical signal intensity, especially in the insular cortex and cingulate gyrus, leptomeningeal enhancement, visualization of the prominent venules, and widespread brain edema. These features may indicate poor prognosis and should alert radiologists to the possibility of acute hepatic encephalopathy in liver transplant recipients and encourage clinicians to prepare appropriate treatment in advance.

Threonine deficiency decreased intestinal immunity and aggravated inflammation associated with NF-κB and target of rapamycin signalling pathways in juvenile grass carp (Ctenopharyngodon idella) after infection with Aeromonas hydrophila.

This study aimed to investigate the impacts of dietary threonine on intestinal immunity and inflammation in juvenile grass carp. Six iso-nitrogenous semi-purified diets containing graded levels of threonine (3·99-21·66 g threonine/kg) were formulated and fed to fishes for 8 weeks, and then challenged with Aeromonas hydrophila for 14 d. Results showed that, compared with optimum threonine supplementation, threonine deficiency (1) decreased the ability of fish against enteritis, intestinal lysozyme activities (except in the distal intestine), acid phosphatase activities, complement 3 (C3) and C4 contents and IgM contents (except in the proximal intestine (PI)), and it down-regulated the transcript abundances of liver-expressed antimicrobial peptide (LEAP)-2A, LEAP-2B, hepcidin, IgZ, IgM and ß-defensin1 (except in the PI) (P<0·05); (2) could up-regulate intestinal pro-inflammatory cytokines TNF-α, IL-1ß, IL-6, IL-8 and IL-17D mRNA levels partly related to NF-κB signalling; (3) could down-regulate intestinal anti-inflammatory cytokine transforming growth factor (TGF)-ß1, TGF-ß2, IL-4/13A (not IL-4/13B) and IL-10 mRNA levels partly by target of rapamycin signalling. Finally, on the basis of the specific growth rate, against the enteritis morbidity and IgM contents, the optimum threonine requirements were estimated to be 14·53 g threonine/kg diet (4·48 g threonine/100 g protein), 15.05 g threonine/kg diet (4·64 g threonine/100 g protein) and 15·17 g threonine/kg diet (4·68 g threonine/100 g protein), respectively.

Relationship between level of plasma ammonia,and changes of serum alpha-fetoprotein,cholinesterase,liver fibrosis index in liver cirrhosis patients with hepatocellular carcinoma in reference to Child-Pugh grades / 中国免疫学杂志

Objective:To investigate the relationship between the level of plasma ammonia(NH3),and the changes of serum alpha-fetoprotein(AFP),cholinesterase(ChE),liver fibrosis index in liver cirrhosis patients with hepatocellular carcinoma(LC-HCC)in reference to Child-pugh grades.Methods: A total of 58 patients with LC and HCC(LC-HCC group),76 patients with LC(LC group)and 60 cases of healthy volunteers(HC group)were collected.Serum AFP were detected by electrochemiluminescence,serum Hyaluronic acid(HA),laminin(LN),type Ⅳ collagen(Ⅳ-C) were detected by chemilu minescence immunoassay,serum ChE were detected by S-Butyrylthiocholine iodide,NH3 was continuously monitored.The levels of AFP,ChE,NH3 and liver fibrosis indexes(HA,LN,Ⅳ-C) among the LC-HCC group,LC group and HC group,different Child-Pugh grades in LC-HCC group were compared.Results: The serum levels of NH3,AFP,HA,LN,Ⅳ-C in LC-HCC group were significantly higher than that in LC and HC group,and ChE levels were significantly reduced,differences between LC group and HC group were statistically significant(P<0.05).With the increase of Child-Pugh grades,the serum levels of NH3,AFP,HA,LN,Ⅳ-C in LC-HCC group were gradually increased but the ChE gradually decreased,the differences were statistically significant(P<0.05).Serum levels of ChE in patients with LC-HCC were significant negatively correlated with Child-Pugh grades,and AFP,NH3,HA,LN,Ⅳ-C were significant positive correlated with Child-Pugh grades(P<0.05).Serum levels of ChE in patients with LC-HCC were significant negatively correlated with LN,Ⅳ-C and HA,while the levels of AFP,NH3 were significant positive correlated with LN,Ⅳ-C and HA(P<0.05).Conclusion: The serum levels of AFP,ChE and NH3 in patients with LC and HCC are significant abnormalities;they are significant positive correlated with Child-Pugh grades;the detection of the these indicators is valuable to non-invasive diagnosis for patients with LC and HCC.

Growth rate, body composition, digestive enzymes and transaminase activities, and plasma ammonia concentration of different weight Jian carp (Cyprinus carpio var. Jian).

The present study investigated the effect of body weight on body composition, digestive and absorptive capacity, transaminase activities in hepatopancreas and muscle, and plasma ammonia concentration of Jian carp (Cyprinus carpio var. Jian). A total of 750 Jian carps (18.0 ± 0.2 g) were randomly distributed into five groups with three replicates and fed the same diet for 56 days. Tissue and plasma samples were collected on days 14, 28, 42, and 56. The results were used to develop a mathematical model for specific growth rate, body moisture and fat content, aspartate transaminase activity and alanine aminotransferase activity in hepatopancreas and muscle, plasma ammonia concentration, and trypsin, chymotrypsin, lipase, and amylase activities in hepatopancreas and intestine, activities of creatine kinase, Na+/K+-ATPase, alkaline phosphatase, and γ-glutamyl transpeptidase in intestine in Jian carp. There were linear relationships between natural logarithms of above indexes and body weight. The body moisture and fat content, digestive and absorptive enzymes activities, and transaminase activities showed negative allometry against body weight of Jian carp which were partial reasons to explain fish growth rate decreasing.

Valproate Induced Hyperammonemic Delirium.

Sodium valproate induced hyperammonaemic delirium with normal liver function tests is a relatively uncommon adverse effect. It may be mistaken for psychosis or worsening of mania leading to wrong diagnosis and improper management. Plasma ammonia levels should be monitored in all patients developing altered mental status after receiving valproate therapy. This is a case series of hyperammonaemic delirium due to valproate reported to the Department of Pharmacology from Department of Psychiatry over a period of one year.

The rate and pattern of urea infusion into the rumen of wethers alters nitrogen balance and plasma ammonia.

Changes in N balance, urinary excretion of purine derivative (PD), urea, creatinine and ammonia and plasma ammonia, glucose, urea, insulin and IGF-1 were examined in four wethers (37 ± 2.6 kg BW). The animals were fitted with permanent ruminal catheters, fed lucerne hay (9.4 MJ/day; 23 g N/day; 7 g soluble N/day, 6 equal meals/day) and treated with contrasting rates of urea infusion into the rumen: first, a continuous infusion (CT), at 3.2 mg urea-N/min for 10 days and then a discontinuous infusion (DT) at 156 mg urea-N/min for 4 min; in 6 daily doses with the meals for 7 days. N balance was calculated from pooled samples of faeces and urine. Jugular blood samples were collected before and 1.5 h after the morning meal (M1) on days CT10, DT2, DT4 and DT6. N retention decreased during DT (p = 0.01) due to a significant increase of N excretion in urine (4 g/day; p = 0.009) and faeces (1 g/day; p = 0.02). Dry matter (p < 0.001) and N digestibility in vivo (p = 0.01) decreased significantly during DT. Urinary urea and PD excretion were not altered by treatment. Significant linear (p = 0.004) and quadratic (p = 0.001) effects were observed for plasma ammonia in M1 (from 170 CT10 to 235 µm DT2 and returned to 120 µm DT6). No changes were observed in plasma glucose, urea, insulin and IGF-1. Results indicate that changes from CT to DT reduced N retention in sheep due to enhanced urinary N excretion, but it was not associated with changes in urinary urea or PD excretion; or plasma concentrations of insulin and IGF-1. As the dry matter (DM) an N digestibility could account a 0.23 of the decrease in N retention; the largest fraction of the reduction in N retention remained unexplained by the results.

Role of plasma ammonia level in detecting intra-abdominal hemorrhage following blunt abdominal trauma.

BACKGROUND: Blunt abdominal injury is a leading cause of death in trauma patients. A reliable test predicting intra-abdominal hemorrhage would be a novel method. The study objective was to assess the diagnostic accuracy of plasma ammonia in detection of intra-abdominal bleeding in patients with blunt abdominal trauma (BAT). MATERIALS AND METHODS: In this observational study, all patients suffering from BAT, referred to our university teaching hospital included. The levels of ammonia were measured at the time of emergency department admission and 1 h after initial treatment. Demographic data, vital signs, and venous blood gas reports were recorded. Findings of contrast-enhanced abdominopelvic computed tomography scan and laparotomy were assumed as a gold standard for abdominal injuries. RESULTS: A total of 104 patients was enrolled in the study. 15 patients (14.4%) had intra-abdominal hemorrhage and the mean plasma ammonia level in this group was significantly higher than the other patients on admission time (101.73 ± 5.41 µg/dL vs. 47.36 ± 26.31 µg/dL, P < 0.001). On receiver-operator characteristic curve analysis, in cutoff point of 89 µg/dL, the sensitivity, specificity, positive and negative likelihood ratios were 100% (95% confidence interval [CI], 79.6-100), 93.26% (95% CI, 86-96.8), 14.83 (95% CI, 6.84-32.12), and 0, respectively. CONCLUSION: The study findings suggest the measurement of ammonia level at the time of admission in the patients with BAT would be a useful test predicting intra-abdominal hemorrhage. Furthermore, decrease in the ammonia level could be a useful marker for monitoring response to treatment in these patients.

Valproate monotherapy induced-delirium due to hyperammonemia: A report of three adult cases with different types of presentation.

One of the important adverse effects of valproate is delirium due to hyperammonemia. In this case report series, we are reporting three cases with interesting and different types of clinical presentation on valproate monotherapy. Valproate-induced delirium may be mistaken for psychosis or worsening of mania leading to improper diagnosis and poor management. We found that there was an elevated level of plasma ammonia in our cases during the delirious state and which decreased when valproate was discontinued. In our cases the serum valproate levels, liver function tests, electroencephalogram, and imaging studies were normal, which were deranged in the previous case reports. We are the first to rechallenge valproate in one of the cases, to prove that valproate caused the hyperammonemia. We suggest that plasma ammonia levels should be monitored routinely in all cases of altered mental status and receiving valproate therapy.

Energy systems during the last spurt (exertion) in an 800-m race / 体力科学

A study was conducted to investigate the relationship between energy systems and running performance, especially during the last spurt in an 800-m race. The subjects were separated into good 800-m runners (group A n=5: best record, 1′54″3±1.4) and a second group of slower 800-m runners (group B n=4: best record, 2′02″1±1.3) . Each group executed two types of running test (600m test and 800m test) . To simulate an 800-m race, the running speed up to 600m was set by means of a lamp pace maker system. The last spurt was running 200m at maximal voluntary running speed. Plasma lactate, plasma ammonia, serum glucose and blood pH were assayed at rest, after warming up, and 6 and 10min after the running test.<BR>The following results were obtained:<BR>1) The last spurt time of group A was significantly faster than that of group B (p<0.01) . 2) In group A, plasma lactate and plasma ammonia concentrations increased significantly during the last spurt (p<0.05) . In group B, however, plasma lactate and plasma ammonia concentrations before the last spurt (600m test values) were very close to the values after the last spurt (800m test values), 3) Last spurt times were significantly related to changes in plasma lactate concentration (r=-0.870, p<0.01) and O<SUP>2</SUP> debt (r=-0.799, p<0.01) during the last spurt.<BR>These results suggest that running performance during the last spurt in an 800-m race depends on anaerobic energy ability, as reflected by plasma lactate, plasma ammonia and O<SUP>2</SUP> debt before the last spurt.