Blood Ammonia Concentration Research Articles

Immunosuppression, oxidative stress, and apoptosis in pig kidney caused by ammonia: Application of transcriptome analysis in risk assessment of ammonia exposure

Ammonia (NH3) is a recognized environmental contaminant around the world and has adverse effects on animal and human health. However, the mechanism of the renal toxicity of NH3 is not well understood. Pigs are considered an ideal model for biomedical and toxicological research because of the similarity to humans in physiological and biochemical basis. Therefore, in this study, twelve pigs were selected as research objects and randomly divided into two groups, namely the control group and the NH3 group. The formal experiment lasted 30 days. The effects of excessive NH3 inhalation on the kidney of fattening pig were evaluated by chemical analysis, ELISA, transcriptome analysis and real-time quantitative PCR (qRT-PCR) from the renal antioxidant level, renal function, blood ammonia content and gene level. Our results showed that excessive NH3 exposure could cause an increase in blood NH3 content, a reduction in renal GSH-Px, SOD and GSH, as well as an increase in MDA levels and an increase in serum creatinine, urea and uric acid levels. In addition, transcriptome analysis showed that NH3 exposure caused changes in 335 differentially expressed genes (DEGs) (including 126 up-regulated DEGs and 109 down-regulated DEGs). Some highly expressed DEGs were enriched into GO terms associated with immune function, oxidative stress, and apoptosis and were verified by qRT-PCR. The qRT-PCR results were comsistent with the transcriptome results. Our results indicated that NH3 exposure could cause changes in renal transcriptional profiles and kidney function, and induce kidney damage in the fattening pigs through oxidative stress, immune dysfunction and apoptosis. Our present study provides novel insights into the immunotoxicity mechanism of NH3 on kidney.

Change in concentration of ammonia and other biochemical indicators in patients with new coronaviral infection

The article demonstrates the results of a study to study the comparative assessment of the concentration of ammonia in the peripheral blood of patients with a viral infection of COVID-19 against the background of previously existing hepatic pathology and without it. There was a correlation between peripheral blood hyperammonemia and an increase in the concentration of markers of acute inflammation. The relationship between a high degree of hyperammonemia and a severe course / death as a result of the development of a new coronavirus infection in the studied patients was traced. The role of the initial chronic hepatic pathology (including non-alcoholic fatty liver disease) as a factor in the unfavorable course of the new coronavirus infection is highlighted.

Production performance, egg quality, plasma biochemical constituents and lipid metabolites of aged laying hens supplemented with incomplete degradation products of galactomannan

This study was conducted to investigate the efficacy of incomplete degradation products of galactomannan (IDPG) on the production performance, egg quality, plasma parameters, and lipid metabolites of laying hens. A total of 288 laying hens were allocated into 4 treatments and fed diets supplemented with 0%, 0.01%, 0.025%, and 0.05% IDPG. Results showed that IDPG supplementation significantly increases egg production and decreases feed conversion ratio (P < 0.05). Eggs laid by hens receiving IDPG exhibited higher eggshell strength (P < 0.05). Moreover, IDPG supplementation significantly increased the serum albumin content, and decreased the blood ammonia content as well as triglyceride levels in serum and liver (P < 0.05). Overall, IDPG can be considered as an effective feed additive due to its capacity of improving egg production, increasing plasma protein, and changing lipid metabolism of laying hens.

Predictive Value of Blood Ammonia in the Prognosis of Acute Liver Failure Evaluated by Receiver Operating Characteristic Curves

To investigate the predictive value of blood ammonia (BLA) quantification in the prognosis of acute liver failure (ALF).Seventy-one patients with ALF were enrolled and BLA concentration was measured in all patients. After following up for 28 days, patients were divided into two groups: the surviving group (n = 21) and the deceased group (n = 50). An independent-samples t-test was used to compare BLA concentrations between the two groups, and receiver operating characteristic curves were used to ¬evaluate the predictive value of BLA in the prognosis of ALF. A fourfold table analysis was performed with the determined BLA cutoff value.The average concentration of BLA in the deceased group was significantly higher compared with the surviving group (144.50 µmol/L vs. 106 µmol/L, respectively; P = .035). The cutoff BLA concentration for a good ALF prognosis was 122.5 µmol/L. The area under the curve was 0.659. Both the sensitivity and specificity were >0.6. The 95% CIs for sensitivity and specificity were 0.452-0.733 and 0.477-0.878, respectively. The fourfold table analysis revealed a positive predictive value of 83.3%, a negative predictive value of 42.9%, a misdiagnosis rate of 28.6%, and an accuracy of 63.4%.With a cutoff BLA concentration of 122.5 µmol/L, the prognosis of ALF could be predicted with high sensitivity and specificity, a positive predictive value, a low misdiagnosis rate, and good accuracy.

The effect of multi-ingredient intra- versus extra-cellular buffering supplementation combined with branched-chain amino acids and creatine on exercise-induced ammonia blood concentration and aerobic capacity in taekwondo athletes

BackgroundThis study aimed to investigate the effect of multi-ingredient intra- (BA) versus extra- (ALK) cellular buffering factor supplementation, combined with the customary intake of branched-chain amino acids (BCAA) and creatine malate (TCM), on body composition, exercise variables, and biochemical and hematological parameters in 9 elite taekwondo athletes.MethodsEight-week randomized double-blind crossover BA (5.0 g·day−1 of β-alanine) versus ALK (0.07 g·kgFFM−1·day−1 of sodium bicarbonate) supplementation combined with BCAA (0.2 g·kgFFM−1·day−1) and TCM (0.05 g·kgFFM−1·day−1) during a standard 8-week taekwondo training period was implemented. In the course of the experiment, body composition (dual X-ray absorptiometry), aerobic capacity (ergospirometric measurements during an incremental treadmill test until exhaustion), and exercise blood biomarkers concentrations were measured. Data were analyzed using repeated measures within-between interaction analysis of variance with the inclusion of experimental supplementation order.ResultsThe maximum post-exercise blood ammonia concentration decreased in both groups after supplementation (from 80.3 ± 10.6 to 72.4 ± 10.2 µmol∙L−1, p = 0.013 in BA; from 81.4 ± 8.7 to 74.2 ± 8.9 µmol∙L−1, p = 0.027 in ALK), indicating reduced exercise-related adenosine triphosphate degradation. However, no differences were found in body composition, aerobic capacity, blood lactate concentration, and hematological parameters after neither BA (combined with BCAA and TCM) nor ALK (combined with BCAA and TCM) supplementation.ConclusionsIn highly trained taekwondo athletes, neither extra- nor intracellular buffering enhancement resulting from BA and ALK supplementation, combined with BCAA and TCM treatment, affects body mass and composition, maximum oxygen uptake, and hematological indices, even though certain advantageous metabolic adaptations can be observed.

A rare thyroid disorder mimicking mitochondrial disease

&amp;lt;p&amp;gt;Introduction. Patients affected with Allan-Herndon-Dudley syndrome (AHDS) have a deficiency of monocarboxylate transporter 8 (MCT8), a protein primarily responsible for the transport of triiodothyronine (T3) into the brain. This X-linked disorder affects almost exclusively males with clinical presentation encompassing developmental delay, axial hypotonia, dystonia, poor head control, quadriplegia and absence of speech. Case reports. Patient 1 is a male child referred to a hospital investigation at 11 months due to severe developmental delay and elevated blood ammonia level (163 mcmol/L). Hypotonia and dystonic movements were noted at admission, with facial dysmorphic features. Laboratory findings revealed increased blood lactate (17.2 mmol/L), alanine (533 mcmol/L) and ammonia (391 mcmol/L) concentrations. Serum creatine-kinase levels showed substantial increase over the course of hospitalization up to 6,855 IU/L. Clinical exome sequencing detected a novel hemizygous frameshift insertion c.1456insC in gene SLC16A2, predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Segregation genetic testing of the family members revealed that mother, maternal uncle and maternal grandmother carry the same mutation in SLC16A2. The boy`s mother experienced learning difficulties through childhood while maternal uncle is severely affected by AHDS. Patient 2 is a boy referred to clinical geneticist due to severe psychomotor delay of unknown etiology. Moderate serum lactate elevation was the only laboratory abnormality during initial investigations. Diagnosis of AHDS was established by clinical exome sequencing, and subsequent hormonal evaluation revealed increased triiodothyronine (T3) level which corresponds well to genetic diagnosis. Conclusion. Presence of lactic acidosis and/or hyperammonemia in children with severe developmental delay is not specific for inborn disorders of energy production, such as mitochondrial disease. Clinicians should consider thyroid hormones profiling in cases of unexplained severe developmental delay in male children, especially if associated with axial hypotonia and dystonic movements.&amp;lt;/p&amp;gt;

Effects of dietary N-carbamylglutamate supplementation on milk production performance, nutrient digestibility and blood metabolomics of lactating Holstein cows under heat stress

Heat stress is a serious threat to dairy cow health worldwide. N-carbamylglutamate (NCG), a novel feed additive, has been applied in dairy cow industry. However, the effects and mechanisms of NCG on dairy cows under heat stress are still unknown. A total of 48 Holstein dairy cows with similar days in milk (154 ± 13.6 d), parity (1-3), and body condition score were randomly divided into 4 groups of 12 animals each. Under heat stress, the cows were fed a TMR diet supplemented with 0 (control), 15, 20, 25 g of NCG/d per cow for 60 days. Milk production performance was recorded and serum parameters were examined. Meanwhile, metabolomics study of plasma based on liquid chromatography-mass spectrometry was also applied to investigate metabolites and pathways in response to NCG supplementation. Milk yield was increased but milk urea nitrogen was reduced by the NCG treatment. Addition of 15 g of NCG/d increased the milk protein percentage compared with the control. No effect of NCG was observed on dry matter intake, lactose percentage, milk fat percentage and somatic cell count. Serum glucose concentrations in cows fed with 15, 20, 25 g of NCG/d were 5.34 ± 0.312, 5.78 ± 0.473 and 5.54 ± 0.711 mmol/L, which were greater than those in the control (4.87 ± 0.367 mmol/L, P < 0.05). Meanwhile, the concentrations of blood urea nitrogen and blood ammonia were decreased with the addition of NCG. Results for antioxidant capacity and immune function showed beneficial effects of NCG, such as the increases in total antioxidant capacity, superoxide dismutase, glutathione peroxidase, IgG, IgM and IgA. Clear separations of plasma metabolic profiles between control and NCG groups were observed in the score plots. Sixteen different metabolites involved in metabolisms of amino acids, ketone bodies, butanoate and energy, as well as gut microbiome-derived metabolism were regulated by NCG supplementation. In conclusion, supplementation with NCG has the potential to enhance production performance, antioxidant capacity and immune function, and improved the metabolic profile of dairy cows under heat stress.

The (in)dependency of blood and sweat sodium, chloride, potassium, ammonia, lactate and glucose concentrations during submaximal exercise

PurposeTo reduce the need for invasive and expensive measures of human biomarkers, sweat is becoming increasingly popular in use as an alternative to blood. Therefore, the (in)dependency of blood and sweat composition has to be explored.MethodsIn an environmental chamber (33 °C, 65% relative humidity; RH), 12 participants completed three subsequent 20-min cycling stages to elicit three different local sweat rates (LSR) while aiming to limit changes in blood composition: at 60% of their maximum heart rate (HRmax), 70% HRmax and 80% HRmax, with 5 min of seated-rest in between. Sweat was collected from the arm and back during each stage and post-exercise. Blood was drawn from a superficial antecubital vein in the middle of each stage. Concentrations of sodium, chloride, potassium, ammonia, lactate and glucose were determined in blood plasma and sweat.ResultsWith increasing exercise intensity, LSR, sweat sodium, chloride and glucose concentrations increased (P ≤ 0.026), while simultaneously limited changes in blood composition were elicited for these components (P ≥ 0.093). Sweat potassium, lactate and ammonia concentrations decreased (P ≤ 0.006), while blood potassium decreased (P = 0.003), and blood ammonia and lactate concentrations increased with higher exercise intensities (P = 0.005; P = 0.007, respectively). The vast majority of correlations between blood and sweat parameters were non-significant (P > 0.05), with few exceptions.ConclusionThe data suggest that sweat composition is at least partly independent of blood composition. This has important consequences when targeting sweat as non-invasive alternative for blood measurements.

Hyperammonemia in azotemic cats.

Hyperammonemia occurs in cats with hepatobiliary and nutritional (cobalamin and arginine deficiency) disorders, and has also been documented in four cats with renal azotemia. We hypothesized that in cats with renal azotemia, fasting hyperammonemia would correlate with indices of worsening kidney function, and would be independent of cobalamin, potassium, systemic inflammation or urinary tract infection (UTI) with urease-producing bacteria. A fasted blood sample was prospectively collected for ammonia and cobalamin analysis from 18 client-owned cats with renal azotemia (creatinine [Cr] ⩾1.6 mg/dl, urine specific gravity <1.030 or documentation of historical chronic kidney disease [CKD]). Correlations between blood ammonia and selected biochemical parameters were analyzed using Pearson's correlation coefficient. Seven castrated males and 11 spayed females with a median age of 12 years (range 4-19 years) were enrolled. Ten of 18 (56%) cats presented for acute kidney injury (AKI) or acute on chronic kidney disease (AoCKD), and 8/18 (44%) presented for progressive CKD. The median Cr was 5.9 mg/dl (range 1.9-24.7 mg/dl). Hyperammonemia was documented in 4/18 (22%) cats, with a median of 95 µmol/dl (range 85-98 µmol/dl), and all four of these cats were classified as AKI/AoCKD. Blood ammonia concentrations had a significant moderate positive correlation between blood urea nitrogen (BUN) (r = 0.645, P = 0.003), Cr (r = 0.578, P = 0.012) and serum phosphorus (r = 0.714, P = 0.0009) but not with cobalamin, potassium or white blood cell count. No cats had UTIs with urease-producing bacteria. A correlation exists between blood ammonia and BUN, Cr and phosphorus in cats with renal azotemia. Future studies are warranted in a larger population of cats to determine the true prevalence, etiology and potential therapeutic effect of medical management of hyperammonemia on long-term prognosis in cats with kidney disease.

Transient hyperammonaemia following epileptic seizures in cats

The aim of this study was to determine whether transient postictal hyperammonaemia exists in cats. The medical records of all feline patients that presented at a Swedish veterinary hospital between 2008 and 2018 were retrospectively reviewed to find those that had a recent or ongoing epileptic seizure. To qualify for inclusion, the medical record had to include information on at least one ammonia value taken in close proximity to, or during, an active seizure, the cat must have exceeded the normal upper limit of blood ammonia concentration on initial testing (reference interval 0-95 μmol/l), and there needed to be a follow-up ammonia value available within a maximum of 3 days. Five cats were included in the study, and they had blood ammonia concentrations on initial testing ranging from 146 to 195 µmol/l. They were all retested within a period of 2 h to 3 days of the original reading. All five cats had a spontaneous decrease in ammonia levels without any specific treatment for hyperammonaemia. Pursuant to the findings of this retrospective study, transient hyperammonaemia may be noted after epileptic seizure in cats. Consequently, a differential diagnostic list in feline patients with hyperammonaemia could, depending on the context, include non-hepatic-related pathologies, such as epileptic seizures.

L-carnitine reduces hospital admissions in patients with hepatic encephalopathy.

The aim of this study was to determine whether oral L-carnitine administration reduces the blood ammonia concentration and number of hospital admissions for hepatic encephalopathy in patients with advanced cirrhosis. Of 68 patients with hepatic encephalopathy treated with oral L-carnitine supplementation from April 2013 to March 2016, we enrolled 19 patients who had received full standard treatment. We analyzed blood ammonia concentration, number of hospital admissions, and prognosis to determine how effective L-carnitine was in achieving mid-term to long-term suppression of recurrent hepatic encephalopathy. Median blood ammonia concentrations at the start, 1 week, 12 weeks, 24 weeks, and 48 weeks were 159, 79, 75, and 82 μg/dL, respectively. Blood ammonia concentrations 12 week, 24 weeks, and 48 weeks after L-carnitine administration were significantly lower than those at the start (P < 0.0001, respectively). During the 3 years prior to oral L-carnitine administration, the enrolled patients were hospitalized a total of 29 times for hepatic encephalopathy. However, during the 3 years following oral L-carnitine administration, they were admitted a total of six times for hepatic encephalopathy (P < 0.001). Median survival time was 40.9 months. Child-Pugh scores before and after oral L-carnitine administration differed significantly, whereas liver reserve function, nutritional status, and muscle index did not change significantly. Oral L-carnitine administration is effective and free of adverse effects in patients with hyperammonemia and reduces the number of hospital admissions for hepatic encephalopathy.

Transportation and handling of blood samples prior to ammonia measurement in the real life of a large university hospital

Background: Hyperammonemia is neurotoxic and as such can be a medical emergency. Preanalytical factors greatly influence the blood ammonia concentration results. Aims and methods: Ammonia concentrations measured in the real life setting of a large hospital after pneumatic transport of blood samples and various time periods before centrifugation were compared to those based on the indications of the reagent manufacturer. In the same routine context, the effects of waiting times of centrifuged samples or after plasma storage at −20 °C and −80 °C were determined. Results: Despite the pneumatic transport, the lead times for sample arrival to the lab were even longer than those recommended for their complete handling until ammonia assay. Ammonia concentration results were not affected by the pneumatic transport of blood samples and by waiting times up to a maximum of 1.75 h before their centrifugation and 1 h after centrifugation. Ammonia stability was superior when plasma was stored at −80 °C. Conclusion: Pneumatic transport and sample handling in the routine practice of our lab do not affect ammonia concentration results provided that waiting times are limited to 1.75 h before and 1 h after centrifugation and samples are kept cold. Otherwise, it is better to freeze plasma at −80 °C.

Involvement of ammonia metabolism in the improvement of endurance performance by tea catechins in mice

Blood ammonia increases during exercise, and it has been suggested that this increase is both a central and peripheral fatigue factor. Although green tea catechins (GTCs) are known to improve exercise endurance by enhancing lipid metabolism in skeletal muscle, little is known about the relationship between ammonia metabolism and the endurance-improving effect of GTCs. Here, we examined how ammonia affects endurance capacity and how GTCs affect ammonia metabolism in vivo in mice and how GTCs affect mouse skeletal muscle and liver in vitro. In mice, blood ammonia concentration was significantly negatively correlated with exercise endurance capacity, and hyperammonaemia was found to decrease whole-body fat expenditure and fatty acid oxidation–related gene expression in skeletal muscle. Repeated ingestion of GTCs combined with regular exercise training improved endurance capacity and the expression of urea cycle–related genes in liver. In C2C12 myotubes, hyperammonaemia suppressed mitochondrial respiration; however, pre-incubation with GTCs rescued this suppression. Together, our results demonstrate that hyperammonaemia decreases both mitochondrial respiration in myotubes and whole-body aerobic metabolism. Thus, GTC-mediated increases in ammonia metabolism in liver and resistance to ammonia-induced suppression of mitochondrial respiration in skeletal muscle may underlie the endurance-improving effect of GTCs.

Effects of α‐ketoglutarate on growth performance, antioxidant capacity and ammonia metabolization against chronic carbonate alkalinity stress in Songpu mirror carp (Cyprinus carpioSongpu)

A 3 × 2 factorial experiment was conducted to investigate the interaction between carbonate alkalinity and dietary α-ketoglutarate (AKG) levels on the growth performance, antioxidant capacity and ammonia metabolization of Songpu mirror carp (Cyprinus carpio Songpu). Each diet (0%, 1% AKG) was randomly allotted to 0 mmol/L, 15 mmol/L, 30 mmol/L carbonate alkalinity groups with three replicate aquaria. The weight gain rate (WGR) significantly increased in the 1% AKG group and significantly decreased with increasing carbonate alkalinity (p < .05). Crude ash was significantly affected by the interaction between carbonate alkalinity and dietary AKG levels and significantly increased in the 1% AKG group (p < .05). A significant interaction between carbonate alkalinity and dietary AKG levels on superoxide dismutase (SOD) activities in hepatopancreas was observed (p < .05). The increasing carbonate alkalinities significantly decreased SOD activities in the hepatopancreas and foregut, catalase (CAT) activities in the hepatopancreas, foregut, midgut and hindgut and glutathione (GSH) contents in the hepatopancreas and foregut (p < .05). Despite AKG addition, the blood ammonia content still increased with increasing carbonate alkalinities. The gene expressions of AQP3, Rhag, Rhcg2 and Na+/K+-ATPase (NKA) in the gills and glutamine synthase (GS) in the brain were significantly upregulated with increasing carbonate alkalinities (p < .05). In the 1% AKG group, GS gene expression significantly upregulated in the brains, whereas AQP3, Rhag, Rhcg2 and NKA gene expressions significantly downregulated in the gills (p < .05). In summary, the 1% AKG addition can enhance the gene expression of ammonia metabolization and improve the antioxidant capacity of Songpu mirror carp with chronic carbonate alkalinity stress.

Rapid Determination of Ammonia in Biological Samples by GC-MS Derivatization Method.

Objective To establish a qualitative and quantitative method to determine ammonia in biological samples by gas chromatography-mass spectrometry （GC-MS）. Methods A heptafluorobutyryl chloride derivatization method was used. GC-MS was used for determination. The effects of different pH conditions, derivatization temperature, time and different extraction solvents on the test results were investigated. The pretreatment conditions were optimized. Results This method could accurately detect the ammonia content in blood, and the limit of detection was determined to be 0.1 μg/mL. The target component showed good linearity in the range of 0.5-200.0 μg/mL （R2=0.987 7）. The relative standard deviation range of intra-day precision was 2.59%-3.88%. The relative standard deviation range of inter-day precision was 3.21%-3.76%. Conclusion The method showed good sensitivity, stability and specificity, therefore can be used for forensic toxicology analysis and clinical biochemical detection.

Effects of histidine load on ammonia, amino acid, and adenine nucleotide concentrations in rats.

The unique capability of proton buffering is the rationale for using histidine (HIS) as a component of solutions for induction of cardiac arrest and myocardial protection in cardiac surgery. In humans, infusion of cardioplegic solution may increase blood plasma HIS from ~ 70 to ~ 21,000µM. We examined the effects of a large intravenous dose of HIS on ammonia and amino acid concentrations and energy status of the body. Rats received 198mM HIS intravenously (20ml/kg) or vehicle. Samples of blood plasma, urine, liver, and soleus (SOL) and extensor digitorum longus (EDL) muscles were analysed at 2 or 24h after treatment. At 2h after HIS load, we found higher HIS concentration in all examined tissues, higher urea and ammonia concentrations in blood and urine, lower ATP content and higher AMP/ATP ratio in the liver and muscles, higher concentrations of almost all examined amino acids in urine, and lower glycine concentration in blood plasma, liver, and muscles when compared with controls. Changes in other amino acids were tissue dependent, markedly increased alanine and glutamate in the blood and the liver. At 24h, the main findings were lower ATP concentrations in muscles, lower concentrations of branched-chain amino acids (BCAA; valine, leucine, and isoleucine) in blood plasma and muscles, and higher carnosine content in SOL when compared with controls. It is concluded that a load of large HIS dose results in increased ammonia levels and marked alterations in amino acid and energy metabolism. Pathogenesis is discussed in the article.

Use Of Quantitative Modelling To Elucidate The Roles Of The Liver, Gut, Kidney, And Muscle In Ammonia Homeostasis And How Lactulose And Rifaximin Alter This Homeostasis.

Humans must eliminate approximately 1M of ammonia per day while maintaining the blood concentration of this potent neurotoxin at a concentration of only about 30 µM. The mechanisms producing such effective ammonia homeostasis are poorly understood by clinicians due to the multiple organs (liver, gut, kidney and muscle) involved in ammonia homeostasis. Based on literature values we present a novel, simplified description of normal and disordered ammonia and the potential mechanisms whereby the drugs used to treat hepatic encephalopathy, lactulose and rifaximin, lower the blood ammonia concentration. Concepts discussed include the following: 1) only about 44 mmol of ammonia/day (4.4% of total production) reaches the peripheral circulation due to the efficient linkage of amino deamination and the urea cycle in hepatic mitochondria; 2) the gut and kidney contribute roughly equally to delivery of this 44 mmol/day to systemic blood; 3) the bulk of gut ammonia production seemingly originates in the small bowel from bacterial deamination of urea by bacteria and mucosal deamination of circulating and ingested glutamine; 4) the apparent production of ammonia in the small bowel markedly exceeds that quantity that enters the portal blood, indicating that ammonia disposal mechanisms in the small bowel play a major role in ammonia homeostasis. With regard to the hyperammonemia of chronic liver disease: 1) shunting of portal blood around the liver, by itself, can account for commonly observed ammonia elevations; 2) severe portal hypertension causes an increased release of ammonia by the kidney; 3) high blood ammonia is associated with an unexplained massive increase in the muscle uptake of ammonia that could play an important role in limiting hyperammonemia; and 4) a major action of lactulose administration may be the enhancement of ammonia uptake by small bowel bacteria, while the mechanism of action of rifaximin is unclear.

P: 9 Pharmacotherapies that Specifically Target Ammonia for the Prevention and Treatment of Hepatic Encephalopathy in Adults With Crrhosis

BACKGROUND: Ammonia plays a key role in the genesis of hepatic encephalopathy (HE). Recent interest has focused on drugs which specifically target ammonia, e.g. sodium benzoate (SB), glycerol phenylbutyrate (GPB), ornithine phenylacetate (OP), AST-120, and polyethylene glycol (PEG). This study aims to evaluate the utility of these pharmacotherapies vs. placebo or non-absorbable disaccharides (NAD), for the management of HE in people with cirrhosis. L-ornithine L-aspartate is not included. METHODS: Electronic/manual searches of the literature were undertaken for relevant RCTs. The results of the meta-analyses are presented as risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CIs). Bias control was assessed using the CHBG domains and the certainty of the evidence using GRADE. RESULTS: Eleven RCTs were identified involving SB (n = 1), GPB (n = 1), OA (n = 2), AST-120 (n = 2) and PEG (n = 3). Treatment periods ranged from five days to 16 weeks. All but one trial was at “high risk of bias”; the certainty of the evidence was very low for all outcomes. Nine trials, with 733 participants, reported blood ammonia concentrations. Significant reductions were observed in placebo-controlled trials evaluating SB (MD −32.00, 95% CI −46.85 to −17.15); GPB (MD −12.00, 95% CI −23.37 to −0.63); OP (MD −27.10, 95% CI −48.55 to −5.65) and AST-120 (MD −22.00, 95% CI −26.75 to −17.25). No significant differences in blood ammonia concentrations were observed when compared to NADs. Eleven trials, with 943 participants, reported mortality data, although there were no events in five trials. No beneficial or harmful effects were found in any of the trials. Seven trials, with 521 participants reported data on HE. Beneficial effects were identified for GPB vs. placebo (RR 0.57, 95% CI 0.36 to 0.90; 178 participants; 1 trial; NNTB = 6) and for PEG vs. lactulose (RR 0.19, 95% CI 0.08 to 0.44; 190 participants; 3 trials; NNTB = 4); no beneficial effects were observed in the remaining three trials with extractable data (Figure 1). Ten trials, with 790 participants, reported a total of 130 serious adverse events. There was no evidence of beneficial or harmful effects of the five agents when compared to placebo or NADs. CONCLUSIONS: These agents generally reduce blood ammonia concentrations, when compared to placebo, but not when compared to NADs. Their overall effects on clinical outcomes of interest and the potential harms associated with their use remain uncertain. Further evidence is needed to fully evaluate their utility in this clinical setting.

The Effect of Beta-Alanine versus Alkaline Agent Supplementation Combined with Branched-Chain Amino Acids and Creatine Malate in Highly-Trained Sprinters and Endurance Athletes: A Randomized Double-Blind Crossover Study.

The study aimed to verify the effect of intra- (beta-alanine—BA) versus extra- (alkaline agents—ALK) cellular buffering agent supplementation, combined with customarily used branched-chain amino acids (BCAAs) and creatine malate (TCM) treatment in natural training conditions. Thirty-one elite athletes (11 sprinters and 20 endurance athletes) participated in the study. Eight-week randomized double-blind, crossover, combined supplementation with BA-ALKplaBCAA&TCM and ALK-BAplaBCAA&TCM was implemented. In the course of the experiment, body composition, aerobic capacity, and selected blood markers were assayed. After BA-ALKplaBCAA&TCM supplementation, total fat-free mass increased in sprinters (p = 0.009). No other differences were found in body composition, respiratory parameters, aerobic capacity, blood lactate concentration, and hematological indices after BA-ALKplaBCAA&TCM/ALK-BAplaBCAA&TCM supplementation. The maximum post-exercise blood ammonia (NH3) concentration decreased in both groups after BA-ALKplaBCAA&TCM supplementation (endurance, p = 0.002; sprint, p < 0.0001). Also, lower NH3 concentrations were observed in endurance athletes in the post-exercise recovery period. The results of our study indicate that combined BCAA, TCM, and BA supplementation is more effective than combined BCAA, TCM and ALK supplementation for an increase in fat-free mass and exercise adaptation, but not for aerobic capacity improvement. Besides, it seems that specific exercise stimuli and the training status are key factors affecting exercise performance, even in athletes using efficient supplementation.

Effect of Immobilized Nitrifying Bacterial Consortium on Ammonia Biodegradation in Aquaculture Pond and Enhanced Growth of Labeo rohita: An In Vitro and In Vivo Studies

This investigation was carried out to remove total ammonia nitrogen (TAN) in aquaculture system by employing immobilized heterotrophic nitrifying bacterial consortium. The bacterial consortium was immobilized on biodegradable and low cost, wood powder. Among the three wood powders tested, Thespesia populnae wood powder showed the highest (99%) nitrifying activity. Nitrifying bacteria immobilized Thespesia populnae wood powder at three different concentrations was applied in a 100-L tank stocked with Labeo rohita for TAN removal. The experiment tanks with the addition of immobilized wood powder were observed TAN concentration below 0.15 ± 0.1 mg/l. This was lower than the control tank without the addition of immobilized wood powder. A highest average body weight gain of Labeo rohita was observed in experiment tanks. The haematology profile in experiment tanks revealed a highest Hb and RBC count, reduction in WBC count and low blood ammonia concentration, which was contrary in control tanks. Histological study showed that severe gill damage occurred in control group, whereas experiment fishes possessed normal gill morphology. The immobilized wood powder was also applied in one hectare aquaculture earthen pond and observed a complete TAN elimination within 24 h. The present study reveals that the heterotrophic nitrifiers immobilized on wood powder could carry out efficient nitrification and thus eliminates TAN from aquaculture pond water and enhances fish growth.