Search Results (8)

Hyperammonaemia in dogs is most frequently associated with hepatic encephalopathy caused by portosystemic shunting. This retrospective multicentre study aimed to investigate the prevalence of hyperammonaemia and hepatic encephalopathy in dogs with recent or ongoing epileptic seizures. Furthermore, we sought to evaluate if transient post-ictal hyperammonaemia as a sequela to seizure activity occurs, as reported in humans and recently in cats. The medical records of all dogs presented between 2014 and 2024 to ten AniCura Veterinary Hospitals in Sweden were retrospectively reviewed to obtain those with recent or ongoing epileptic seizures with concurrent analysis of ammonia. The records of 267 dogs were extracted for further review. Inclusion criteria included information regarding the description and characterisation of the seizures and the analysis of ammonia within 24 h after last reported seizure activity. Additionally, hepatic function tests were required in dogs with elevated ammonia. In total, 58 dogs fulfilled the inclusion criteria, and 10 of those dogs (17%) had hyperammonaemia. Three dogs had documented hepatopathy, and two of them had surgically corrected portosystemic shunts. In seven dogs, no definitive cause of hyperammonaemia could be established. Three of the seven dogs had no evidence of portosystemic shunts, and six had no laboratory evidence supporting acute liver failure. According to the findings in this retrospective study, hyperammonaemia in the absence of evident acute hepatic failure or portosystemic shunting can occur in dogs with epileptic seizures, indicating that other differentials than hepatic encephalopathy should be considered. This study could not confirm the hypothesis of hyperammonaemia being a transient consequence of seizures. Full article

Point-of-care (POC) tests for blood ammonia (BA) measurement have not been well evaluated in veterinary species. This cross-sectional study sought to establish an inferred reference interval for BA using a POC analyser in dogs and cats. Blood ammonia was measured in 175 dogs and 63 cats for which relevant clinical history and laboratory data was available. Reference values were inferred based on comparisons between patients with and without disease pathologies reported to cause BA elevation. Descriptive statistics, Pearson Chi², and Mann–Whitney U testing were used to assess for associations between clinical parameters and BA concentration. Seventy-one percent (124/175) of dogs and forty-six percent (29/63) of cats had undetectable BA. Following the exclusion of dogs with potential causes of hyperammonaemia, all remaining dogs had BA < 30 µg/dL. With one exception, all dogs with BA > 30 µg/dL had liver disease. All dogs with a clinical suspicion of hepatic encephalopathy (HE) had BA > 40 µg/dL. Following the exclusion of cats with potential causes of hyperammonaemia, all remaining cats had BA < 25 µg/dL. Only 50% of cats with BA > 25 µg/dL had liver disease. All cats with a clinical suspicion of HE had BA > 30 µg/dL. Based on this study population, BA < 30 µg/dL and <25 µg/dL should be considered normal in dogs and cats, respectively. Additionally, dogs with BA > 30 µg/dL are likely to have liver disease, while cats with BA > 25 µg/dL appear to exhibit a wider variety of disease pathologies. Full article

Two different diets able to induce dietary hyperammonaemia (a methionine–choline-deficient (MCD) diet and a methionine-deficient diet enriched with ammonium acetate (MAD + 20% ammonium acetate)) were tested in a rat model. The diets were shown to have different modes of action, inducing significant hyperammonaemia (HA) and growth retardation in the rats, with different metabolic consequences. The MCD diet resulted in the development of endogenous HA, with a decrease in bilirubin levels and an increase in hepatic fat content. In contrast, the MAD + 20% ammonium acetate diet increased circulating ALP and haptoglobin levels and decreased liver mass. The above results suggest that the MCD diet deteriorated the liver function of the rats, resulting in the development of endogenous HA, while the MAD diet caused moderate changes in liver metabolism, resulting in the development of exogenous HA. Interestingly, the commonly used oral treatments Lactulose and Rifaximin did not ameliorate hyperammonaemia during or after the treatment period. In conclusion, even though the diets used in the current study caused somewhat similar hyperammonaemia, they seemed to provoke different metabolic consequences. The latter can have an impact on the severity of the resulting hyperammonaemia and thus on the hyperammonaemia-induced encephalopathy, resulting in the development of distinguishing cognitive and metabolic (liver) effects compared to other forms of encephalopathy. We hypothesized that these rat models, with significantly increased serum ammonia levels, along with different liver injuries, could serve as a suitable double animal model for the testing of new, oral enzyme therapies for hepatic encephalopathy in future studies. Full article

Ammonia (NH₃) has been shown to be a key biomarker for a wide variety of diseases, such as hepatic and chronic kidney diseases (CKD), and cancers. It also has relevance to the oral health research area, and, hence, its determination in appropriate biofluids and tissues is of much importance. However, since it contains exchangeable >N-H protons, its analysis via ¹H NMR spectroscopy, which is a widely employed technique in untargeted metabolomic studies, is rendered complicated. In this study, we focused on the ¹H NMR analysis of this biomarker in less invasively collected human saliva samples, and we successfully identified and quantified it as ammonium cation (NH₄⁺) in post-collection acidulated forms of this biofluid using both the standard calibration curve and standard addition method (SAM) approaches. For this purpose, n = 27 whole mouth saliva (WMS) samples were provided by healthy human participants, and all donors were required to follow a fasting/oral environment abstention period of 8 h prior to collection. Following acidification (pH 2.00), diluted WMS supernatant samples treated with 10% (v/v) D₂O underwent ¹H NMR analysis (600 MHz). The acquired results demonstrated that NH₄⁺ can be reliably determined in these supernatants via integration of the central line of its characteristic 1:1:1 intensity triplet resonance (complete spectral range δ = 6.97–7.21 ppm). Experiments performed also demonstrated that any urease-catalysed NH₃ generation occurring post-sampling in WMS samples did not affect the results acquired during the usual timespan of laboratory processing required prior to analysis. Further experiments demonstrated that oral mouth-rinsing episodes conducted prior to sample collection, as reported in previous studies, gave rise to major decreases in salivary NH₄⁺ levels thereafter, which renormalised to only 50–60% of their basal control concentrations at the 180-min post-rinsing time point. Therefore, the WMS sample collection method employed significantly affected the absolute levels of this analyte. The LLOD was 60 μmol/L with 128 scans. The mean ± SD salivary NH₄⁺ concentration of WMS supernatants was 11.4 ± 4.5 mmol/L. The potential extension of these analytical strategies to the screening of other metabolites with exchangeable ¹H nuclei is discussed, as is their relevance to the monitoring of human disorders involving the excessive generation and/or uptake of cellular/tissue material, or altered homeostasis, in NH₃. Full article

X-linked ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle defect. The disease severity ranges from asymptomatic carrier state to severe neonatal presentation with hyperammonaemic encephalopathy. We audited the diagnosis and management of OTCD, using an online 12-question-survey that was sent to 75 metabolic centres in Turkey, France and the UK. Thirty-nine centres responded and 495 patients were reported in total. A total of 208 French patients were reported, including 71 (34%) males, 86 (41%) symptomatic and 51 (25%) asymptomatic females. Eighty-five Turkish patients included 32 (38%) males, 39 (46%) symptomatic and 14 (16%) asymptomatic females. Out of the 202 UK patients, 66 (33%) were male, 83 (41%) asymptomatic and 53 (26%) symptomatic females. A total of 19%, 12% and 7% of the patients presented with a neonatal-onset phenotype in France, Turkey and the UK, respectively. Vomiting, altered mental status and encephalopathy were the most common initial symptoms in all three countries. While 69% in France and 79% in Turkey were receiving protein restriction, 42% were on a protein-restricted diet in the UK. A total of 76%, 47% and 33% of patients were treated with ammonia scavengers in Turkey, France and the UK, respectively. The findings of our audit emphasize the differences and similarities in manifestations and management practices in three countries. Full article

Hyperammonaemia is a metabolic derangement that may cause severe neurological damage and even death due to cerebral oedema, further complicating the prognosis of its triggering disease. In small children it is a rare condition usually associated to inborn errors of the metabolism. As age rises, and especially in adults, it may be precipitated by heterogeneous causes such as liver disease, drugs, urinary infections, shock, or dehydration. In older patients, it is often overlooked, or its danger minimized. This protocol was drafted to provide an outline of the clinical measures required to normalise ammonia levels in patients of all ages, aiming to assist clinicians with no previous experience in its treatment. It is an updated protocol developed by a panel of experts after a review of recent publications. We point out the importance of frequent monitoring to assess the response to treatment, the nutritional measures that ensure not only protein restriction but adequate caloric intake and the need to avoid delays in the use of specific pharmacological therapies and, especially, extrarenal clearance measures. In this regard, we propose initiating haemodialysis when ammonia levels are >200–350 µmol/L in children up to 18 months of age and >150–200 µmol/L after that age. Full article

Hyperammonaemic encephalopathy in adults is a rare condition in the absence of liver disease and is associated with a high mortality and risk of permanent neurological deficits. Seldomly, the condition is caused by an inborn error of metabolism in the urea cycle, triggered by an exogenic factor such as gastrointestinal haemorrhage, gastric bypass surgery, starvation, seizures, vigorous exercise, burn injuries, or drugs hampering the elimination of ammonia. Here, we present a fatal case of an unrecognized genetic ornithine transcarbamylase deficiency (OTCD) presenting with a subacute progressive encephalopathy. We review the current literature and discuss the differential diagnosis and treatment options. As swift diagnosis and initiation of treatment is vital, awareness of hyperammonaemic encephalopathy and its possible causes can help improve the prognosis of this condition. Full article

C-type natriuretic peptide (CNP) is the major natriuretic peptide of the central nervous system and acts via its selective guanylyl cyclase-B (GC-B) receptor to regulate cGMP production in neurons, astrocytes and endothelial cells. CNP is implicated in the regulation of neurogenesis, axonal bifurcation, as well as learning and memory. Several neurological disorders result in toxic concentrations of ammonia (hyperammonaemia), which can adversely affect astrocyte function. However, the relationship between CNP and hyperammonaemia is poorly understood. Here, we examine the molecular and pharmacological control of CNP in rat C6 glioma cells and rat GPNT brain endothelial cells, under conditions of hyperammonaemia. Concentration-dependent inhibition of C6 glioma cell proliferation by hyperammonaemia was unaffected by CNP co-treatment. Furthermore, hyperammonaemia pre-treatment (for 1 h and 24 h) caused a significant inhibition in subsequent CNP-stimulated cGMP accumulation in both C6 and GPNT cells, whereas nitric-oxide-dependent cGMP accumulation was not affected. CNP-stimulated cGMP efflux from C6 glioma cells was significantly reduced under conditions of hyperammonaemia, potentially via a mechanism involving changed in phosphodiesterase expression. Hyperammonaemia-stimulated ROS production was unaffected by CNP but enhanced by a nitric oxide donor in C6 cells. Extracellular vesicle production from C6 cells was enhanced by hyperammonaemia, and these vesicles caused impaired CNP-stimulated cGMP signalling in GPNT cells. Collectively, these data demonstrate functional interaction between CNP signalling and hyperammonaemia in C6 glioma and GPNT cells, but the exact mechanisms remain to be established. Full article