Blood Ammonia Concentration Research Articles

Workload and spirometry associated with untethered swimming in horses

BackgroundSwimming has been used empirically for rehabilitation and conditioning of horses. However, due to challenges imposed by recording physiological parameters in water, the intensity of free swimming effort is unknown.ObjectivesMeasure the physiological workload associated with untethered swimming in horses.Five fit Arabian endurance horses were assessed while swimming in a 100 m-long indoor pool. Horses were equipped with a modified ergospirometry facemask to measure oxygen consumption (V̇O2) and ventilatory parameters (inspired/expired volumes, VI, VE; peak inspiratory/expiratory flows, PkVI, PkVE; respiratory frequency, Rf; minute ventilation, VE; inspiratory/expiratory durations and ratios, tI, tE, tI/ttot, tE/ttot); and an underwater electrocardiogram that recorded heart rate (HR). Postexercise venous blood lactate and ammonia concentrations were measured. Data are reported as median (interquartile ranges).ResultsHorses showed bradypnea (12 breaths/min (10–16)) for the first 30 s of swimming. V̇O2 during swimming was 43.2 ml/(kg.min) (36.0–56.6). Ventilatory parameters were: VI = 16.7 L (15.3–21.8), VE = 14.7 L (12.4–18.9), PkVI = 47.8 L/s (45.8–56.5), PkVE = 55.8 L/s (38.3–72.5), Rf = 31.4 breaths/min (20.0–33.8), VE = 522.9 L/min (414.7–580.0), tI = 0.5 s (0.5–0.6), tE = 1.2 s (1.1–1.6), tI/ttot = 0.3 (0.2–0.4), tE/ttot = 0.7 (0.6–0.8). Expiratory flow tracings showed marked oscillations that coincided with a vibrating expiratory sound. HR was 178.0 bpm (148.5–182.0), lactate = 1.5 mmol/L (1.0–1.9) and ammonia = 41.0 µmol/L (36.5–43.5).ConclusionsFree (untethered) swimming represents a submaximal, primarily aerobic exercise in horses. The breathing pattern during swimming is unique, with a relatively longer apneic period at the beginning of the exercise and an inspiratory time less than half that of expiration.

Summer scour syndrome in weaned dairy calves: case series

BackgroundSummer scour syndrome (SSS) is a recently identified pathological condition affecting weaned dairy and dairy-beef calves during their first grazing season in Ireland. The syndrome is characterised by diarrhoea, weight loss, weakness, and can ultimately lead to death in some calves. Oral and oesophageal ulcerations are present in some cases. This study aimed to characterise a series of SSS cases in weaned dairy-bred calves on Irish commercial farms.ResultsFive farms with calves having unexplained diarrhoea at grass were referred by private veterinary practitioners (PVP) following preliminary testing to exclude coccidiosis and parasitic gastroenteritis. Farms were visited within 2 to 5 days following PVP’s referrals, or 2 days to 3 weeks relative to the onset of clinical signs. Farm management data, grass and concentrate samples, and biological samples from 46 calves (8 to 10 calves/farm) displaying clinical signs were collected. Two farms were subsequently found positive for coccidiosis and/or had chronic pneumonia problems after a thorough herd investigation and were designated as non-case farms (NCF). The remaining three farms were deemed typical SSS outbreaks (case farms; CF). Mean rumen fluid pH per farm ranged from 6.67 to 7.09 on CF, and 6.43–6.88 on NCF. Mean rumen fluid ammonia concentrations ranged from 17.6 to 29.6 mg/L and 17.2–45.0 mg/L on CF and NCF, respectively. Corresponding blood ammonia concentrations ranged from 129 to 223 µmol/L and 22–25 µmol/L. Mean blood copper and molybdenum concentrations were within normal range on all farms. Grass crude protein concentrations on the paddocks where the calves had grazed, and were currently grazing on the day of visit ranged from 137 to 148 g/kg DM and 106–177 g/kg DM, respectively on CF, and 160–200 g/kg DM and 151–186 g/kg DM, respectively on NCF. On CF, inorganic nitrogen fertiliser was applied 1 to 3 weeks pre-grazing, whereas on the two NCF, inorganic nitrogen fertiliser was applied 2 to 3 weeks pre-grazing on one farm and no fertiliser was applied on the other.ConclusionThese findings suggest that copper or molybdenum toxicity, and ruminal acidosis are not the primary causes of SSS. High blood ammonia concentrations and the timing and level of inorganic nitrogen fertiliser application to paddocks pre-grazing, warrant further investigation.

Effect of Guanidinoacetic Acid Supplementation on Growth Performance, Rumen Fermentation, Blood Indices, Nutrient Digestion, and Nitrogen Metabolism in Angus Steers

Guanidinoacetic acid (GAA) functions as a precursor for creatine synthesis in the animal body, and maintaining ample creatine reserves is essential for fostering rapid growth. This study aimed to explore the impact of GAA supplementation on growth performance, rumen fermentation, blood indices, nutrient digestion, and nitrogen metabolism in Angus steers through two experiments: a feeding experiment (Experiment 1) and a digestive metabolism experiment (Experiment 2). In Experiment 1, thirty-six Angus steers (485.64 ± 39.41 kg of BW) at 16 months of age were randomly assigned to three groups: control (CON), a conventional dose of GAA (CGAA, 0.8 g/kg), and a high dose of GAA (HGAA, 1.6 g/kg), each with twelve steers. The adaptation period lasted 14 days, and the test period was 130 days. Weighing occurred before morning feeding on days 0, 65, and 130, with rumen fluid and blood collected before morning feeding on day 130. Experiment 2 involved fifteen 18-month-old Angus steers (575.60 ± 7.78 kg of BW) randomly assigned to the same three groups as in Experiment 1, with a 7-day adaptation period and a 3-day test period. Fecal and urine samples were collected from all steers during this period. Results showed a significantly higher average daily gain (ADG) in the CGAA and HGAA groups compared to the CON group (p = 0.043). Additionally, the feed conversion efficiency (FCE) was significantly higher in the CGAA and HGAA groups than in the CON group (p = 0.018). The concentrations of acetate and the acetate:propionate ratio were significantly lower in the CGAA and HGAA groups, while propionate concentration was significantly higher (p < 0.01). Serum concentration of urea (UREA), blood ammonia (BA), GAA, creatine, and catalase (CAT) in the CGAA and HGAA groups were significantly higher than in the CON group, whereas malondialdehyde (MDA) concentrations were significantly lower (p < 0.05). Digestibility of dry matter (DM) and crude protein (CP) and the nitrogen retention ratio were significantly higher in the CGAA and HGAA groups than in the CON group (p < 0.05). In conclusion, dietary addition of both 0.8 g/kg and 1.6 g/kg of GAA increased growth performance, regulated rumen fermentation and blood indices, and improved digestibility and nitrogen metabolism in Angus steers. However, higher doses of GAA did not demonstrate a linear stacking effect.

Newly discovered variants in unexplained neonatal encephalopathy.

The genetic background of neonatal encephalopathy (NE) is complicated and early diagnosis is beneficial to optimizing therapeutic strategy for patients. NE Patients with unclear etiology received regular clinical tests including ammonia test, metabolic screening test, amplitude-integrated electroencephalographic (aEEG) monitoring, brain Magnetic Resonance Imaging (MRI) scanning, and genetic test. The protein structure change was predicted using Dynamut2 and RoseTTAFold. 15 out of a total of 113 NE Patients were detected with newly reported pathogenic variants. In this sub-cohort, (1) seizure was the primary initial symptoms; (2) four patients had abnormal metabolic screening results, and two of them were also diagnosed with excessive blood ammonia concentration; (3) the brain MRI results were irregular in three infants and the brain waves were of moderate-severe abnormality in about a half of the patients. The novel pathogenic variants discovered in this study belonged to 12 genes, and seven of them were predicted to introduce a premature translation termination. In-silicon predictions showed that four variants were destructive to the protein structure of KCNQ2. Our study expands the mutation spectrum of genes associated with NE and introduces new evidence for molecular diagnosis in this newborn illness.

Metabolic adaptation of the clam Ruditapes philippinarum during air exposure and the positive effects of sodium nitroprusside pretreatment.

The Manila clam (Ruditapes philippinarum), as one of the shellfish living in the intertidal zone, is known for its strong ability to withstand air exposure. Sodium nitroprusside (SNP), a donor of nitric oxide (NO), has been shown to be useful for antioxidant and immune regulation in aquatic animals. In this study, an untargeted metabolomics (LC-MS/MS) technique was employed for the first time in Manila clam to analyze the metabolic and histological impacts after air exposure and the positive effects of SNP pretreatment. During air exposure, a significant increase in taurine, L-glutamate, and several polyunsaturated fatty acids in clams was detected, which indicates that clams may experience inflammatory reactions, oxidative stress, and an increase in blood ammonia content. When clams were exposed to SNP for 6h, arginine, spermine, L-glutamic acid, and glutathione content were all upregulated, indicating that the SNP exposure induced NO production and improved antioxidant capacity in clams. When the clams were exposed to air after SNP pretreatment, there were no significant differences in the levels of taurine, L-glutamate, or aliphatic acids between the experimental and control groups. Gill tissue was more severely damaged in clams directly exposed to air than in those that experienced air exposure after SNP pretreatment, especially in clams exposed to air for a long time (72h). Both metabolomics and tissue section structure indicated that SNP pretreatment decreased the stress responses caused by air exposure in R. philippinarum. These findings provided fresh insights and a theoretical foundation for understanding the tolerance to air exposure and physiological functions of SNP (or NO) in R. philippinarum.

Combination of tea catechins and ornithine effectively activates the urea cycle: an in vitro and human pilot study.

Accumulation of ammonia causes central and peripheral fatigue. This study aimed to investigate the synergistic effect of tea catechins and low-dose ornithine in activating the urea cycle to reduce blood ammonia levels during exercise. We used hepatocyte-like cells derived from human-induced pluripotent stem (iPS) cells to assess the effect of tea catechins combined with ornithine on urea cycle activity. The urea production and expression of key genes involved in the metabolism of urea were investigated. We then examined the synergistic improvement in ammonia metabolism by tea catechins in combination with ornithine in a human pilot study. Tea catechins combined with ornithine increased urea cycle activity in hepatocyte-like cells derived from human iPS cells. Intake of 538.6mg of tea catechins with 1592mg of ornithine for 2 consecutive days during exercise loading suppressed the exercise-induced increase in the blood ammonia concentration as well as stabilized blood glucose levels. Controlling the levels of ammonia, a toxic waste produced in the body, is important in a variety of situations, including exercise. The present study suggests that a heterogeneous combination of polyphenols and amino acids efficiently suppresses elevated ammonia during exercise in humans by a mechanism that includes urea cycle activation. This study was registered in the University Hospital Medical Information Network Clinical Trial Registry (No. UMIN000035484, dated January 8, 2019).

Spectroscopic Based Ammonia Measurement System

This article describes the design and implementation of a microcontroller-based system for determining ammonia concentrations in blood. By adding a blood sample to a test strip, the proposed system induces a series of reactions known as Berthelot's response, resulting in an accurate change in strip color. A current is then generated when the photodiode detects the 635 nm wavelength reflected off the strip. An op-amp is used to convert the current to voltage. Because of their ease of use and software flexibility, microcontrollers are recognized as important components in modern electronics. The concentration of (NH3) is determined by a microcontroller depending on the voltage value. The test results are shown on an LCD or recorded in data files. Any normal or abnormal outcomes are appropriately recorded by the system. A PC software program is written to accept and save data. The proposed system is initially designed using the concepts of Software Analysis and Design; the process of building the proposed systems begins with determining the system's requirements, working on the analysis, using the best design techniques according to the software Engineering process, and finally modeling it on an electronic board before being realized and implemented. It is used in biomedical measurements. It is also handy for monitoring and researching final circuits.

A functional evaluation of anti-fatigue and exercise performance improvement following vitamin B complex supplementation in healthy humans, a randomized double-blind trial.

B vitamins play a crucial role in maintaining fundamental cellular functions and various essential metabolic pathways in the body. Although they do not directly provide energy, each B vitamin acts as a cofactor in energy metabolism processes. Based on the evidence presented above, we hypothesized that a 28-day supplementation of vitamin B would enhance physical performance and reduce physical fatigue. The objective of this study was to evaluate the anti-fatigue effect of vitamin B supplementation, specifically vitamin B1, B2, B6, and B12, and its potential to improve exercise performance. We employed a randomized double-blind crossover design with a 28-day supplementation period. Sixteen male and sixteen female subjects, aged 20-30 years, were divided into two groups: the placebo group (n=16, equal gender distribution) and the Ex PLUS® group (n=16, equal gender distribution). The participants received either placebo or Ex PLUS® (one tablet per day) for 28 consecutive days. Following the intervention, there was a 14-day wash-out period during which the subjects did not receive any further interventions. After supplementation with Ex PLUS®, we found a significant increase in the running time by 1.26-fold (p < 0.05) to exhaustion compared to that before supplementation and that in the placebo group. In addition, the Ex PLUS® supplementation group presented significantly reduced blood lactate and blood ammonia concentrations during exercise and at rest after exercise compared with placebo (p < 0.05). In conclusion, 28 consecutive days of vitamin B complex (Ex PLUS®) supplementation significantly improved exercise endurance performance and reduced exercise fatigue biochemical metabolites in not athletes. In addition, it does not cause adverse effects in humans when taken at appropriate doses.

Blood Ammonia Concentration in Children with Chronic Liver Disease: A Tool for Prediction of Esophageal Varices

Background: Esophageal varices (EVs) are a serious complication of portal hypertension in patient with chronic liver disease (CLD). The major portion of ammonia carried by portal blood is shunted into systemic circulation in chronic liver disease. The upper GI endoscopy is currently the best reliable method to diagnose the presence of esophageal varices. But it is invasive, relatively expensive and not easily available. Blood ammonia is a noninvasive and easily accessible laboratory parameter that can predict the presence of esophageal varices.&#x0D; Objectives: To observe the blood ammonia concentration in children with chronic liver disease: a tool for prediction of esophageal varices.&#x0D; Methods: This cross sectional observational study was conducted at the Department of Paediatric Gastroenterology and Nutrition, BSMMU, Dhaka, Bangladesh from January 2018 to December 2019. A total of 63 cases of CLD were selected. Study sample were selected according to the inclusion and exclusion criteria. Along with proper clinical history, examination &amp; initial investigation, fasting venous blood ammonia level and upper GI endoscopy were done in all patients. Receiver-Operator Characteristic (ROC) curve was analysis to set up a cut-off value of blood ammonia for prediction of esophageal varices. Sensivity, specificity, positive predictive value, negative predictive value and accuracy were determined to see the performance of blood ammonia value as a diagnostic test for esophageal varices.&#x0D; Results: Among the 63 patients, (74.6%) had esophageal varices. Wilson disease was the most common etiology of CLD (43; 68.3%) among the studied patients. The mean blood ammonia level were 40.5± 18.0 (µmol/L), 50.5± 14.3 (µmol/L), 50.7± 9.9 (µmol/L), 53.1± 26.9 (µmol/L) and 71.9± 19.0 (µmol/L) in absent esophageal varices, grade-I, grade-II, grade-III and grade-IV esophageal varices respectively. The difference was statistically significant (&lt;0.05). Moderate correlation (r= 0.452; p value = 0.001) between blood ammonia level and grades of esophageal varices was found. It was observed that wasting of thenar and hypothenar muscle was the most common stigmata, seen in 15 (23.8%) cases, 2 (3.2%) had clubbing, 7 (11.1%) had leuconychia, 1 (1.6%) had palmer erythema, 3 (4.8%) had gynacomasia and 1 (1.6%) had testicular atrophy. Wilson disease was the most common 43 (68.3%). It was observed that 45 (71.4 %) patients had raised serum ALT and 45 (71.4%) had low serum albumin (&lt;3.5 g/dl). Low haemoglobin (&lt;9 gm/dl) was found in 47 (74.6%) cases, raised serum bilirubin level (&gt;1.2 mg/dl) in 29 (46.03%) cases, thrombocytopenia (platelet count &lt;1.50×109/mm3) in 36 (57.1%) patients and prolonged INR (&gt;1.5) in 29 (46.03%) cases, blood ammonia was raised (&gt;32 µmol/L) in 52 (82.5%) cases. It was observed that the mean ± SD blood ammonia level was 56.2± 17.9 µmol/L in esophageal varices present group (n = 47) and 40.5± 18.0 µmol/L in absent esophageal varices group (n = 16). Here p value is 0.004, which is statistically significant.&#x0D; Conclusion: Blood ammonia concentration is a biochemical predictor for assessing the grading of esophageal varices. In the present study, a moderate positive correlation was found between blood ammonia concentration and grades of esophageal varices in children with CLD.

Long-Term Effects of Rifaximin on Patients with Hepatic Encephalopathy: Its Possible Effects on the Improvement in the Blood Ammonia Concentration Levels, Hepatic Spare Ability and Refractory Ascites.

Background and Objectives: To investigate the long-term efficacy of rifaximin (RFX) for hyperammonemia and efficacy for refractory ascites in patients with cirrhosis. Materials and Methods: We enrolled 112 patients with liver cirrhosis who were orally administered RFX in this study. Changes in the clinical data of patients were evaluated up to 36 months after RFX administration. The primary endpoint was a change in blood ammonia levels. Secondary endpoints included changes in clinical symptoms, Child–Pugh (CP) score, number of hospitalizations, degree of refractory ascites, adverse events, and the relationship between RFX administration and the renin-angiotensin-aldosterone system. Results: An improved rate of overt hepatic encephalopathy (HE) of 82.7% was observed 3 months after RFX administration, which significantly induced a progressive decrease in blood ammonia concentration and an improved CP score up to 36 months. No serious RFX treatment-related adverse events were observed. 36.5% in patients after RFX administration improved refractory ascites. After RFX administration, patients with satisfactory control of hepatic ascites without addition of diuretic had lower renin concentration than those with poor control (p < 0.01). At less than 41 pg/mL renin concentration, the control of refractory ascites was significantly satisfactory (p < 0.0001). Conclusions: RFX reduced blood ammonia concentration and improved hepatic spare ability and the quality of life of patients with long-term HE to up to 36 months. Our study revealed the effects of RFX against refractory ascites, suggesting that renin concentration may be a predictive marker for assessing ascites control.

Biochemical testing for inborn errors of metabolism: experience from a large tertiary neonatal centre

Inborn errors of metabolism are an individually rare but collectively significant cause of mortality and morbidity in the neonatal period. They are identified by either newborn screening programmes or clinician-initiated targeted biochemical screening. This study examines the relative contribution of these two methods to the identification of inborn errors of metabolism and describes the incidence of these conditions in a large, tertiary, neonatal unit. We also examined which factors could impact the reliability of metabolic testing in this cohort. This is a retrospective, single-site study examining infants in whom a targeted metabolic investigation was performed from January 2018 to December 2020 inclusive. Data was also provided by the national newborn screening laboratory regarding newborn screening diagnoses. Two hundred and four newborns received a clinician-initiated metabolic screen during the time period examined with 5 newborns being diagnosed with an inborn error of metabolism (IEM) (2.4%). Of the 25,240 infants born in the hospital during the period examined, a further 11 newborns had an inborn error of metabolism diagnosed on newborn screening. This produced an incidence in our unit over the time described of 6.34 per 10,000 births. This number reflects a minimum estimate, given that the conditions diagnosed refer to early-onset disorders and distinctive categories of IEM only. Efficiency of the clinician-initiated metabolic screening process was also examined. The only statistically significant variable in requiring repeat metabolic screening was early day of life (z-score = − 2.58, p = 0.0098). A total of 28.4% was missing one of three key metabolic investigation parameters of blood glucose, ammonia or lactate concentration with ammonia the most common investigation missing. While hypoglycemia was the most common clinical rationale for a clinician-initiated metabolic test, it was a poor predictor of inborn error of metabolism with no newborns of 25 screened were diagnosed with a metabolic disorder.Conclusion: Clinician-targeted metabolic screening had a high diagnostic yield given the relatively low prevalence of inborn errors of metabolism in the general population. Thoughts should be given to the rationale behind each targeted metabolic test and what specific metabolic disease or category of inborn error of metabolism they are concerned along with commencing targeted testing.What is Known:• Inborn errors of metabolism are a rare but potentially treatable cause of newborn mortality and morbidity.• A previous study conducted in a tertiary unit in an area with limited newborn screening demonstrated a diagnostic yield of 5.4%.What is New:• Clinician-initiated targeted metabolic screening has a good diagnostic performance even with a more expanded newborn screening programme.• Further optimisation could be achieved by examining the best timing and also the rationale of metabolic testing in the newborn period.

Moving towards a novel therapeutic strategy for hyperammonemia that targets glutamine metabolism.

Patients with urea cycle disorders intermittently develop episodes of decompensation with hyperammonemia. Although such an episode is often associated with starvation and catabolism, its molecular basis is not fully understood. First, we attempted to elucidate the mechanism of such starvation-associated hyperammonemia. Using a mouse embryonic fibroblast (MEF) culture system, we found that glucose starvation increases ammonia production, and that this increase is associated with enhanced glutaminolysis. These results led us to focus on α-ketoglutarate (AKG), a glutamate dehydrogenase inhibitor, and a major anaplerotic metabolite. Hence, we sought to determine the effect of dimethyl α-ketoglutarate (DKG), a cell-permeable AKG analog, on MEFs and found that DKG mitigates ammonia production primarily by reducing flux through glutamate dehydrogenase. We also verified that DKG reduces ammonia in an NH4 Cl-challenged hyperammonemia mouse model and observed that DKG administration reduces plasma ammonia concentration to 22.8% of the mean value for control mice that received only NH4 Cl. In addition, we detected increases in ornithine concentration and in the ratio of ornithine to arginine following DKG treatment. We subsequently administered DKG intravenously to a newborn pig with hyperammonemia due to ornithine transcarbamylase deficiency and found that blood ammonia concentration declined significantly over time. We determined that this effect is associated with facilitated reductive amination and glutamine synthesis. Our present data indicate that energy starvation triggers hyperammonemia through enhanced glutaminolysis and that DKG reduces ammonia accumulation via pleiotropic mechanisms both in vitro and in vivo. Thus, cell-permeable forms of AKG are feasible candidates for a novel hyperammonemia treatment.

Progesterone regulates inflammation and receptivity of cells via the NF-κB and LIF/STAT3 pathways

A high concentration of blood ammonia can lead to failure of early embryo implantation in dairy cows. Progesterone (P4) is an important hormone that regulates the changes of uterine receptivity and participates in pregnancy during early implantation. However, whether P4 alleviates the harmful effects of blood ammonia is unknown. Therefore, this experiment treated bovine endometrial epithelial cells (BEEC) with ammonia chloride and P4. The results showed that ammonia decreased the viability of BEEC, upregulated the ROS level and apoptosis rate, and upregulated the expressions of Bax, Bcl-2, P53, Cyt-c, caspase-3, caspase-8 and caspase-9. It also upregulated the expressions of TLR4, NF-κB, and in turn, produced a large amount of IL-6 and downregulated the expressions of EGF and VEGF. After co-treating BEEC with ammonia and P4, P4 had no alleviating effect on cell viability, ROS and apoptosis, but downregulated the expressions of TLR4, NF-κB, IL-6, and upregulated the expressions of LIF, EGF and VEGF. Inhibition of STAT3 signaling pathway, LIF expression was not affected, and VEGF expression was down-regulated. Using LIF treated BEEC, VEGF expression was upregulated, but after the addition of inhibitors, the expression of VEGF was not upregulated by LIF. Therefore, progesterone could not alleviate the oxidative stress and apoptosis induced by ammonia in BEEC. However, progesterone ameliorated the inflammation and receptivity genes of BEEC induced by ammonia via the NF-κB and LIF/STAT3 signaling pathways.

The effects of acute and chronic oral L-arginine supplementation on exercise-induced ammonia accumulation and exercise performance in healthy young men: A randomised, double-blind, cross-over, placebo-controlled trial

Background/ObjectivesThis study examined the effects of a single and chronic oral intake of l-arginine supplementation on blood ammonia concentration and exercise performance. MethodsSixteen healthy young men (mean ± standard deviation, 23 ± 3 years) participated in a randomised, double-blind, cross-over, placebo-controlled study. For the acute trials, the participants consumed 200 mL of water containing either l-arginine (5 g) or placebo (dextrin; 5.5 g) and performed cycling exercise at 75% of heart rate reserve for 60 min, followed by a 15-min cycling performance test. For the chronic trials, the participants continued to consume each designated supplement twice a day for another 13 days, and then repeated the same protocol as the acute trials at day 15. After a 14-day washout period, the participants changed the supplement and repeated the same protocol as above. ResultsPlasma ammonia concentrations were lower in the chronic arginine trial than those in both acute placebo (mean difference - 4.5 μmol/L) and acute arginine (mean difference - 5.1 μmol/L) trials (p < 0.05). There was no difference in plasma ammonia concentration between the chronic arginine and chronic placebo trials (mean difference - 1.2 μmol/L). No differences were found in mean power output during the performance test between the chronic arginine and chronic placebo trials (mean difference 0.5 W) or between the acute arginine and acute placebo trials (mean difference 0.0 W). ConclusionsAn acute and chronic oral intake of l-arginine supplementation did not attenuate exercise-induced increases in ammonia accumulation or had no significant impact on cycling performance.

Different dehydration levels and their impact on blood ammonia, cognitive-motor performance, and muscle damage in acclimated runners.

Prolonged exercise in the heat can promote dehydration, which could impair ammonia metabolism, cognitive-motor performance, and muscle damage. However, exercise heat acclimation induces physiological adaptations that improve performance, metabolism, and cellular protection. This study aimed to evaluate different dehydration levels and their impact on blood ammonia, cognitive-motor performance, and muscle damage after a race in the heat in acclimated runners. Sixteen male amateur endurance runners performed a half marathon race. After the race, the runners were divided into two groups according to their percentage body mass change (Δ% BM): Δ% BM less than 3% (G1%; N.=8) and Δ% BM greater than or equal to 3% (G3%; N.=8). Hydration status, biochemical parameters, and cognitive-motor performance were assessed before and after the race. Blood ammonia concentrations were increased in both G1% (before: 46±26 µmol/L; after: 118±22 µmol/L) and G3% (before: 41±15 µmol/L; after: 108±15 µmol/L) groups. There was an early increase in all markers of muscle damage (creatine kinase [CK], lactate dehydrogenase [LDH], aspartate aminotransferase [AST], and alanine aminotransferase [ALT]) in both groups, but only LDH was greater in the G3% group than in the G1% group. Cognitive-motor performance did not differ between groups. Dehydration up to ~4% BM loss does not affect blood ammonia concentrations and cognitive-motor performance in acclimated runners. The results also suggest that exercising in the heat induces the early appearance of several markers of muscle damage in acclimated runners regardless of hydration status.

Evaluation of L-Selenomethionine on Ameliorating Cardiac Injury Induced by Environmental Ammonia

L-Selenomethionine is one of the important organic selenium sources. The supplementation of L-selenomethionine in diets is significant to improve the health of pigs. Ammonia is a major pollutant in the atmosphere and piggery, posing a threat to human and animal health. Although ammonia exposure can damage the heart, the mechanism of cardiac toxicity by ammonia is still unknown. In this study, we investigated the mechanism of cardiac injury induced by ammonia exposure in pigs and the protective effect of L-selenomethionine on its cardiotoxicity. The results showed that the blood ammonia content of pig increased significantly in ammonia group, the expressions of energy metabolism-related genes (LDHA, PDK4, HK2, and CPTIB) and the oxidative stress indexes were significantly changed (P < 0.05), the AMPK/PPAR-γ/NF-κB signaling pathways were activated, the chromatin edge aggregation and nuclear pyknosis were observed in ultrastructure, the apoptotic cells were significantly increased (P < 0.05), and the mRNA and protein expressions of apoptosis-related genes (Bcl-2, Bax, Cyt-c, caspase-3, and caspase-9) were significantly affected (P < 0.05). The above changes were significantly alleviated in ammonia + L-selenomethionine group, but there were still significant differences compared with the C group (P < 0.05). Our results indicated that ammonia exposure could cause energy metabolism disorder and oxidative stress and induce apoptosis of cardiomyocytes through AMPK/PPAR-γ/NF-κB pathways, which could lead to cardiac injury and affect cardiac function. L-Selenomethionine could effectively alleviate the cardiac damage caused by ammonia and antagonize the cardiotoxicity of ammonia.

Alleviative effect of melatonin on the decrease of uterine receptivity caused by blood ammonia through ROS/NF-κB pathway in dairy cow

High concentration of blood ammonia can affect the uterus receptivity and decrease fecundity in dairy cow. Melatonin can reduce reactive oxygen species (ROS) level and has antioxidant and anti-inflammatory effects. However, it is not clear whether melatonin can alleviate ammonia-induced apoptosis of endometrial epithelial cell (EEC) and reduced uterus receptivity. The bovine EEC were treated with ammonium chloride and/or melatonin. Cell viability, apoptosis, oxidative stress and mitochondrial membrane potential were measured and the expression of apoptosis-related genes (p53, Cyt-c, Bax, Bcl-2, caspase-8, caspase-9 and caspase-3), uterus receptivity related genes (VEGF, LIF and EGF) and inflammatory factors (TLR-4, IL-6 and NF-κB) were detected. In addition, the expression of VEGF was detected after adding NF-κB inhibitor (40 μM) and IL-6 (1 ng/mL and 50 ng/mL). The results showed that ammonia significantly increased intracellular ROS level, mRNA and protein expression of Bax, p53, Cyt-c, caspase-9, caspase-8, caspase-3, TLR-4, NF-κB and IL-6, promoted cell apoptosis, while decreased mitochondrial membrane potential, the mRNA and protein expression of VEGF and EGF. Interestingly, melatonin significantly mitigated ammonia-induced changes. However, melatonin could not alleviate ammonia-induced changes of IL-6 and VEGF when NF-κB signal pathway was inhibited. The addition of IL-6 significantly reduced mRNA and protein expression of VEGF. In conclusion, ammonia induced EEC apoptosis through ROS production and activation of mitochondrial apoptosis pathway, and induced inflammatory response through TLR4/NF-κB/IL-6 pathway. Melatonin alleviated EEC apoptosis by inhibiting ROS pathway, and reduced IL-6 expression by inhibiting TLR-4/NF-κB signal pathway, which eventually improved VEGF expression and uterus receptivity in dairy cows.

Relationship between heat storage and parameters of thermotolerance and fatigue in exertional heat stress

Background/Aim. The risk assessment of heat illness and fatigue development is essential in military service. The aim of our study was to investigate the relationship between heat storage and various psychophysiological parameters of heat stress, as well as potential peripheral markers of fatigue in soldiers performing exertional heat stress tests. Methods. Fifteen young, healthy, and unacclimatized men underwent an exertional heat stress test (EHST) with the submaximal workload in warm conditions (WBGT 29?C) in a climatic chamber. Every 10 min, the following parameters of thermotolerance were measured or calculated: core temperature (Tc), mean skin (Tsk) and body temperature (Tb), heart rate (HR), heat storage (HS), physiological strain index (PSI), as well as peripheral markers of fatigue [blood concentrations of ammonia, urea nitrogen (BUN), lactate dehydrogenase (LDH), cortisol and prolactin] and subjective parameters: thermal sensation (TS) and rate of perceived exertion (RPE). Results. Tolerance time varied from 45 to 75 min (mean 63 ? 7.7 min). Average values of Tc, Tb, and HR constantly increased during EHST, while Tsk reached the plateau after 10 min. Concentrations of all investigated peripheral markers of fatigue were significantly higher after EHST compared to baseline levels (31.47 ? 7.29 vs. 11.8 ? 1.11 ?mol/L for ammonia; 5.92 ? 0.73 vs. 4.69 ? 0.74 mmol/L for BUN, 187.27 ?2 8.49 vs.152.7 3? 23.39 U/L for LDH, 743.43 ? 206.19 vs. 558.79 ? 113.34 mmol/L for cortisol, and 418.08 ? 157.14 vs. 138.79 ? 92.83 ?IU/mL for prolactin). Conclusions. This study demonstrates the relationship between heat storage and Tc, HR, TS, and RPE, but also with PSI. Concentrations of cortisol and especially prolactin showed a significant correlation with parameters of thermotolerance.

Effects of Resistance Training to Muscle Failure on Acute Fatigue: A Systematic Review and Meta-Analysis.

Proper design of resistance training (RT) variables is a key factor to reach the maximum potential of neuromuscular adaptations. Among those variables, the use of RT performed to failure (RTF) may lead to a different magnitude of acute fatigue compared with RT not performed to failure (RTNF). The fatigue response could interfere with acute adaptive changes, in turn regulating long-term adaptations. Considering that thelevel of fatigue affects long-term adaptations, it is important to determine how fatigue is affected by RTF versus RTNF. The aim of this systematic review and meta-analysis was to compare the effects of RTF versus RTNF on acute fatigue. The search was conducted in January 2021 in seven databases. Only studies with a crossover design that investigated the acute biomechanical properties (vertical jump height, velocity of movement, power output,or isometric strength), metabolic response (lactate or ammonia concentration), muscle damage (creatine kinase activity), and rating of perceived exertion (RPE) were selected. The data (mean ± standard deviation and sample size) were extracted from the included studies and were either converted into the standardized mean difference (SMD) or maintained in the raw mean difference (RMD) when the studies reported the results in the same scale. Random-effects meta-analyses were performed. Twenty studies were included in the systematic review and 12 were included in the meta-analysis. The main meta-analyses indicated greater decrease of biomechanical properties for RTF compared with RTNF(SMD - 0.96, 95% confidence interval [CI] - 1.43 to - 0.49,p < 0.001). Furthermore, there was a larger increase in metabolic response(RMD 4.48 mmol·L-1, 95% CI 3.19-5.78,p < 0.001), muscle damage(SMD 0.76, 95% CI 0.31-1.21,p = 0.001), and RPE(SMD 1.93, 95% CI 0.87-3.00,p < 0.001) for RTF compared with RTNF. Further exploratory subgroup analyses showed that training status (p = 0.92), timepoint (p = 0.89), load (p = 0.10), and volume (p = 0.12) did not affect biomechanical properties; however, greater loss in the movement velocity test occurred on upper limbs compared with lower limbs (p < 0.001). Blood ammonia concentration was greater after RTF than RTNF (RMD 44.66 μmol·L-1, 95% CI 32.27-57.05,p < 0.001), as was 48h post-exercise blood creatine kinase activity(SMD 0.86, 95% CI 0.33-1.42,p = 0.002). Furthermore, although there was considerable heterogeneity in the overall analysis (I2 = 83.72%; p < 0.01), a significant difference in RPE after RTF compared with RTNF was only found for studies that did not equalize training volumes. In summary, RTF compared with RTNF led to a greater decrease in biomechanical properties and a simultaneous increase in metabolic response, higher muscle damage, and RPE. The exploratory analyses suggested a greater impairment in the velocity of movement test for the upper limbs, more pronounced muscle damage 48h post-exercise, and a greater RPE in studies with non-equalized volume after the RTF session compared with RTNF. Therefore, it can be concluded that RTF leads to greater acute fatigue compared with RTNF. The higher acute fatigue after RTF can also have an important impact on chronic adaptive processes following RT; however, the greater acute fatigue following RTF can extend the time needed for recovery, which should be considered when RTF is used. The original protocol was prospectively registered (CRD42020192336) in the International Prospective Register of Systematic Reviews (PROSPERO).

Hyperammonemia in Inherited Metabolic Diseases.

Ammonia is a neurotoxic compound which is detoxified through liver enzymes from urea cycle. Several inherited or acquired conditions can elevate ammonia concentrations in blood, causing severe damage to the central nervous system due to the toxic effects exerted by ammonia on the astrocytes. Therefore, hyperammonemic patients present potentially life-threatening neuropsychiatric symptoms, whose severity is related with the hyperammonemia magnitude and duration, as well as the brain maturation stage. Inherited metabolic diseases caused by enzymatic defects that compromise directly or indirectly the urea cycle activity are the main cause of hyperammonemia in the neonatal period. These diseases are mainly represented by the congenital defects of urea cycle, classical organic acidurias, and the defects of mitochondrial fatty acids oxidation, with hyperammonemia being more severe and frequent in the first two groups mentioned. An effective and rapid treatment of hyperammonemia is crucial to prevent irreversible neurological damage and it depends on the understanding of the pathophysiology of the diseases, as well as of the available therapeutic approaches. In this review, the mechanisms underlying the hyperammonemia and neurological dysfunction in urea cycle disorders, organic acidurias, and fatty acids oxidation defects, as well as the therapeutic strategies for the ammonia control will be discussed.