Showing papers on "Urea cycle published in 2017"
TL;DR: It is demonstrated that postmortem human brain urea levels are elevated in a larger cohort of HD cases, including those with low-level neuropathology (Vonsattel grade 0/1), which indicates increased protein catabolism, possibly as an alternate energy source given the generalized metabolic defect in HD.
Abstract: The neurodegenerative disorder Huntington’s disease (HD) is typically characterized by extensive loss of striatal neurons and the midlife onset of debilitating and progressive chorea, dementia, and psychological disturbance. HD is caused by a CAG repeat expansion in the Huntingtin (HTT) gene, translating to an elongated glutamine tract in the huntingtin protein. The pathogenic mechanism resulting in cell dysfunction and death beyond the causative mutation is not well defined. To further delineate the early molecular events in HD, we performed RNA-sequencing (RNA-seq) on striatal tissue from a cohort of 5-y-old OVT73-line sheep expressing a human CAG-expansion HTT cDNA transgene. Our HD OVT73 sheep are a prodromal model and exhibit minimal pathology and no detectable neuronal loss. We identified significantly increased levels of the urea transporter SLC14A1 in the OVT73 striatum, along with other important osmotic regulators. Further investigation revealed elevated levels of the metabolite urea in the OVT73 striatum and cerebellum, consistent with our recently published observation of increased urea in postmortem human brain from HD cases. Extending that finding, we demonstrate that postmortem human brain urea levels are elevated in a larger cohort of HD cases, including those with low-level neuropathology (Vonsattel grade 0/1). This elevation indicates increased protein catabolism, possibly as an alternate energy source given the generalized metabolic defect in HD. Increased urea and ammonia levels due to dysregulation of the urea cycle are known to cause neurologic impairment. Taken together, our findings indicate that aberrant urea metabolism could be the primary biochemical disruption initiating neuropathogenesis in HD.
70 citations
TL;DR: It is found that the mitochondrial form of arginase (ARG2), which hydrolyzes arginine into ornithine and urea, is induced upon obesity, and silencing or loss of ARG2 markedly suppresses PDA.
Abstract: Obesity is an established risk factor for pancreatic ductal adenocarcinoma (PDA). Despite recent identification of metabolic alterations in this lethal malignancy, the metabolic dependencies of obesity-associated PDA remain unknown. Here we show that obesity-driven PDA exhibits accelerated growth and a striking transcriptional enrichment for pathways regulating nitrogen metabolism. We find that the mitochondrial form of arginase (ARG2), which hydrolyzes arginine into ornithine and urea, is induced upon obesity, and silencing or loss of ARG2 markedly suppresses PDA. In vivo infusion of 15N-glutamine in obese mouse models of PDA demonstrates enhanced nitrogen flux into the urea cycle and infusion of 15N-arginine shows that Arg2 loss causes significant ammonia accumulation that results from the shunting of arginine catabolism into alternative nitrogen repositories. Furthermore, analysis of PDA patient tumors indicates that ARG2 levels correlate with body mass index (BMI). The specific dependency of PDA on ARG2 rather than the principal hepatic enzyme ARG1 opens a therapeutic window for obesity-associated pancreatic cancer.
65 citations
TL;DR: This review aims to provide extensive insights on potential roles of ornithine in many of the disease related cellular processes and also on the structural features of Ornithine interacting proteins, enabling development of therapeutic modalities.
59 citations
TL;DR: Significant increases in urea, arginine, citrulline, asymmetric and symmetric dimethylarginine, alongside decreases in sphingolipids, indicate that both the urea cycle and nitric oxide pathways are dysregulated at early stages in HD.
Abstract: The pronounced cachexia (unexplained wasting) seen in Huntington’s disease (HD) patients suggests that metabolic dysregulation plays a role in HD pathogenesis, although evidence of metabolic abnormalities in HD patients is inconsistent. We performed metabolic profiling of plasma from presymptomatic HD transgenic and control sheep. Metabolites were quantified in sequential plasma samples taken over a 25 h period using a targeted LC/MS metabolomics approach. Significant changes with respect to genotype were observed in 89/130 identified metabolites, including sphingolipids, biogenic amines, amino acids and urea. Citrulline and arginine increased significantly in HD compared to control sheep. Ten other amino acids decreased in presymptomatic HD sheep, including branched chain amino acids (isoleucine, leucine and valine) that have been identified previously as potential biomarkers of HD. Significant increases in urea, arginine, citrulline, asymmetric and symmetric dimethylarginine, alongside decreases in sphingolipids, indicate that both the urea cycle and nitric oxide pathways are dysregulated at early stages in HD. Logistic prediction modelling identified a set of 8 biomarkers that can identify 80% of the presymptomatic HD sheep as transgenic, with 90% confidence. This level of sensitivity, using minimally invasive methods, offers novel opportunities for monitoring disease progression in HD patients.
59 citations
TL;DR: In livers of mice, FXR regulates amino acid catabolism and detoxification of ammonium via ureagenesis and glutamine synthesis and binds to regulatory sites of genes encoding these proteins in control livers.
52 citations
TL;DR: Overall, liver involvement, such as acute liver failure or steatotic-like disease, which may evolve toward cirrhosis, has been reported in all six main UCDs.
Abstract: Urea cycle disorders (UCDs) are inborn errors of metabolism of the nitrogen detoxification pathway and encompass six principal enzymatic deficiencies. The aging of UCD patients leads to a better knowledge of the long-term natural history of the condition and to the reporting of previously unnoticed manifestations. Despite historical evidence of liver involvement in UCDs, little attention has been paid to this organ until recently. Hence, we reviewed the available scientific evidence on acute and chronic liver dysfunction and liver carcinogenesis in UCDs and discuss their pathophysiology. Overall, liver involvement, such as acute liver failure or steatotic-like disease, which may evolve toward cirrhosis, has been reported in all six main UCDs. Excessive glycogen storage is also a prominent histologic feature, and hypoglycemia has been reported in citrin deficiency. Hepatocarcinomas seem frequent in some UCDs, such as in citrin deficiency, and can sometimes occur in non-cirrhotic patients. UCDs may differ in liver involvement according to the enzymatic deficiency. Ornithine transcarbamylase deficiency may be associated more with acute liver failure and argininosuccinic aciduria with chronic liver failure and cirrhosis. Direct toxicity of metabolites, downstream metabolic deficiencies, impaired tricarboxylic acid cycle, oxidative stress, mitochondrial dysfunction, energy deficit, and putative toxicity of therapies combine in various ways to cause the different liver diseases reported.
47 citations
TL;DR: Future studies are needed to corroborate the presence of secondary carnitine deficiency among children with EED and to understand how these metabolic derangements may negatively affect the growth and development of young children.
40 citations
TL;DR: Overall, as ammonia-scavenging drugs are usually safe and well tolerated among cancer patients, further studies should be instigated to explore the role of these drugs in liver cancer, and it is proposed that ammonia- scaventing drugs might also be used to non-invasively probe liver glutamine metabolism in vivo.
Abstract: Introduction: Ammonia-scavenging drugs, benzoate and phenylacetate (PA)/phenylbutyrate (PB), modulate hepatic nitrogen metabolism mainly by providing alternative pathways for nitrogen disposal.Areas covered: We review the major findings and potential novel applications of ammonia-scavenging drugs, focusing on urea cycle disorders and liver disease.Expert opinion: For over 40 years, ammonia-scavenging drugs have been used in the treatment of urea cycle disorders. Recently, the use of these compounds has been advocated in acute liver failure and cirrhosis for reducing hyperammonemic-induced hepatic encephalopathy. The efficacy and mechanisms underlying the antitumor effects of these ammonia-scavenging drugs in liver cancer are more controversial and are discussed in the review. Overall, as ammonia-scavenging drugs are usually safe and well tolerated among cancer patients, further studies should be instigated to explore the role of these drugs in liver cancer. Considering the relevance of glutamine m...
39 citations
TL;DR: The results establish skeletal muscle glycogen as the source of TCA cycle expansion that normally accompanies exercise and imply that impaired T CA cycle flux is a central mechanism of restricted oxidative capacity in this disorder.
Abstract: McArdle disease and mitochondrial myopathy impair muscle oxidative phosphorylation (OXPHOS) by distinct mechanisms: the former by restricting oxidative substrate availability caused by blocked glycogen breakdown, the latter because of intrinsic respiratory chain defects. We applied metabolic profiling to systematically interrogate these disorders at rest, when muscle symptoms are typically minimal, and with exercise, when symptoms of premature fatigue and potential muscle injury are unmasked. At rest, patients with mitochondrial disease exhibit elevated lactate and reduced uridine; in McArdle disease purine nucleotide metabolites, including xanthine, hypoxanthine, and inosine are elevated. During exercise, glycolytic intermediates, TCA cycle intermediates, and pantothenate expand dramatically in both mitochondrial disease and control subjects. In contrast, in McArdle disease, these metabolites remain unchanged from rest; but urea cycle intermediates are increased, likely attributable to increased ammonia production as a result of exaggerated purine degradation. Our results establish skeletal muscle glycogen as the source of TCA cycle expansion that normally accompanies exercise and imply that impaired TCA cycle flux is a central mechanism of restricted oxidative capacity in this disorder. Finally, we report that resting levels of long-chain triacylglycerols in mitochondrial myopathy correlate with the severity of OXPHOS dysfunction, as indicated by the level of impaired O2 extraction from arterial blood during peak exercise. Our integrated analysis of exercise and metabolism provides unique insights into the biochemical basis of these muscle oxidative defects, with potential implications for their clinical management.
33 citations
TL;DR: In vivo and ex vivo evidence of a urea cycle metabolic phenotype in a prodromal HD mouse model is reported and a hypothesis that mutant HTT leads to a selective deficiency of neuronal Mn at an early disease stage, contributing to HD striatal urea-cycle pathophysiology through an effect on arginase activity is supported.
29 citations
TL;DR: Urea and prolactin concentrations are decreased, fT4 concentration is increased in aqueous humor of keratoconus patients, and uric acid concentration remains unchanged, suggesting metabolic disorder and hormonal balance may both have an impact on keratconus development.
Abstract: Purpose: Keratoconus is a noninflammatory disease of the cornea associated with progressive thinning and conical shape. Metabolic alterations in the urea cycle, with changes in collagen fibril stability, oxidative stress, thyroid hormones and prolactin with regulatory effect on biosynthesis and biomechanical stability of corneal stroma, may all play a role in keratoconus etiology. Our purpose was to determine urea, uric acid, prolactin and free thyroxin (fT4) concentrations in human aqueous humor (hAH) of keratoconus and cataract patients.Methods: hAH was collected from 100 keratoconus (penetrating keratoplasty) (41.9 ± 14.9 years, 69 males) and 100 cataract patients (cataract surgery) (71.2 ± 12.4 years, 58 males). Urea, uric acid, prolactin and fT4 concentrations were measured by Siemens clinical chemistry or immunoassay system. For statistical analysis, a generalized linear model (GLM) was used.Results: Urea concentration was 11.88 ± 3.03 mg/dl in keratoconus and 16.44 ± 6.40 mg/dl in cataract ...
TL;DR: In this paper, Tributyl phosphate (TBP) was used to identify differential endogenous metabolites, draw network metabolic pathways and conduct network analysis to elucidate the underlying mechanisms involved in TBP induced pathological changes of the liver.
TL;DR: The models obtained in this study could be used in feeding models to predict urea recycling and thus to improve formulation of diets to reduce N losses that contribute to air and water pollution.
Abstract: In ruminants, urea recycling is considered an evolutionary advantage. The amount of urea recycled mainly depends of the nitrogen (N) intake and the amount of organic matter (OM) digested in the rumen. Because recycled N contributes to meeting microbial N requirements, accurate estimates of urea recycling can improve the understanding of efficiency of N utilization and N losses to the environment. The objective of this study was to evaluate urea kinetics and microbial usage of recycled urea N in ruminants using a meta-analytical approach. Treatment mean values were compiled from 25 studies with ruminants (beef cattle, dairy cows and sheep) which were published from 2001 to 2016, totalling 107 treatment means. The data set was analyzed according to meta-analysis techniques using linear or non-linear mixed models, taking into account the random variations among experiments. Urea N synthesized in the liver (UER) and urea N recycled to the gut (GER) linearly increased (P<0.001) as N intake (g/BW0.75) increased, with increases corresponding to 71.5% and 35.2% of N intake, respectively. The UER was positively associated (P<0.05) with dietary CP concentration and the ratio of CP to digestible OM (CP:DOM). Maximum curvature analyses identified 17% dietary CP as the point where there was a prominent increase in hepatic synthesis of urea N, likely due to an excess of dietary N leading to greater ammonia absorption. The GER:UER decreased with increasing dietary CP concentration (P<0.05). At dietary CP⩾19%, GER:UER reached near minimal values. The fraction of UER eliminated as urinary urea N and the contribution of urea N to total urinary N were positively associated with dietary CP (P<0.05), both reaching values near the plateau when dietary CP was 17%. The fractions of GER excreted in the feces and utilized for anabolism decreased, whereas the fraction of GER returned to the ornithine cycle increased with dietary CP concentration (P<0.05). Recycled urea N assimilated by ruminal microbes (as a fraction of GER) decreased as dietary CP and CP:DOM increased (P<0.05). The efficiency of microbial assimilation of recycled urea N was near plateau values at 194 g CP/kg DOM. The models obtained in this study contribute to the knowledge on N utilization, and they could be used in feeding models to predict urea recycling and thus to improve formulation of diets to reduce N losses that contribute to air and water pollution.
TL;DR: Carnitine supplementation was useful for reversal of a woman with epilepsy who developed hyperammonemia after a change in her anticonvulsant therapy, allowing her to continue valproic acid for seizure control.
Abstract: Valproic acid is a broad-spectrum anticonvulsant that has also gained attention in the psychiatric setting. With respect to safety, valproic acid may induce a seemingly rare condition, hyperammonemia, which can induce a wide variety of symptoms ranging from irritability to coma. The proposed mechanism of hyperammonemia involves depletion of carnitine and overproduction of a toxic metabolite, 4-en-valproic acid, both of which impair the urea cycle and thus ammonia elimination. Carnitine is a commonly used antidote for acute intoxication of valproic acid, but is not a therapeutic option for management of chronic adults with adverse effects related to valproic acid. We herein report a case involving a woman with epilepsy who developed hyperammonemia after a change in her anticonvulsant therapy. She reported increased seizures and gastrointestinal disturbances. Her ammonia, valproic acid, 4-en-valproic acid, and carnitine levels were monitored. Her ammonia level was elevated and her carnitine level was at the inferior limit of the population range. She was supplemented with carnitine at 1 g/day. After 1 month, her ammonia level decreased, her carnitine level increased, and her seizures were better controlled. Carnitine supplementation was useful for reversal of her hyperammonemia, allowing her to continue valproic acid for seizure control.
TL;DR: Liver transplant should be considered in patients with UCD with a MAC of ≥300 μmol/L at the time of disease onset, and LT may have prevented further neurodevelopmental complications in children with MAC ≥300 μg/L compared with non‐transplant management.
Abstract: UCDs are among the most common inherited metabolic diseases in Japan. We investigated the clinical manifestations, treatment, and prognoses of 177 patients with UCDs who were evaluated and treated from January 1999 to March 2009 in Japan, using a questionnaire survey. Among these 177 patients, 42 (seven with carbamoyl phosphate synthetase 1 deficiency, 27 with ornithine transcarbamylase deficiency, seven with argininosuccinate synthetase deficiency, and one with arginase 1 deficiency) underwent living-donor LT. Although this study was retrospective and included limited neurodevelopmental information before and after LT, we evaluated whether LT could improve neurodevelopmental outcomes in patients with UCDs. The neurodevelopmental outcomes of patients with a MAC of <300 μmol/L at the time of onset were not significantly different between the LT and non-LT groups (P=.222). LT may have prevented further neurodevelopmental complications in children with MAC ≥300 μmol/L (P=.008) compared with non-transplant management. Therefore, Liver transplant should be considered in patients with UCD with a MAC of ≥300 μmol/L at the time of disease onset.
TL;DR: A 63‐year‐old man with alcoholic cirrhosis who underwent orthotopic liver transplantation, gradual worsening of his mental status, and progressive elevation of ammonia levels is presented, raising concern for a donor‐derived metabolic disorder of the urea cycle.
TL;DR: Testosterone replacement reduces protein loss and hepatic urea synthesis and is concluded that testosterone regulates whole-body protein metabolism by suppressing the urea cycle.
Abstract: CONTEXT The urea cycle is a rate-limiting step for amino acid nitrogen elimination. The rate of urea synthesis is a true indicator of whole-body protein catabolism. Testosterone reduces protein and nitrogen loss. The effect of testosterone on hepatic urea synthesis in humans has not been studied. OBJECTIVE To determine whether testosterone reduces hepatic urea production. DESIGN An open-label study. PATIENTS AND INTERVENTION Eight hypogonadal men were studied at baseline, and after two weeks of transdermal testosterone replacement (Testogel, 100 mg/day). MAIN OUTCOMES MEASURES The rate of hepatic urea synthesis was measured by the urea turnover technique using stable isotope methodology, with 15N2-urea as tracer. Whole-body leucine turnover was measured, from which leucine rate of appearance (LRa), an index of protein breakdown and leucine oxidation (Lox), a measure of irreversible protein loss, were calculated. RESULTS Testosterone administration significantly reduced the rate of hepatic urea production (from 544.4 ± 71.8 to 431.7 ± 68.3 µmol/min; P < 0.01), which was paralleled by a significant reduction in serum urea concentration. Testosterone treatment significantly reduced net protein loss, as measured by percent Lox/LRa, by 19.3 ± 5.8% (P < 0.05). There was a positive association between Lox and hepatic urea production at baseline (r2 = 0.60, P < 0.05) and after testosterone administration (r2 = 0.59, P < 0.05). CONCLUSION Testosterone replacement reduces protein loss and hepatic urea synthesis. We conclude that testosterone regulates whole-body protein metabolism by suppressing the urea cycle.
TL;DR: These studies provide proof-of-concept for gene-editing at the Arg1 locus and highlight the challenges that lie ahead to restore sufficient liver-based urea cycle function in patients with Urea cycle disorders.
Abstract: Arginase-1 deficiency in humans is a rare genetic disorder of metabolism resulting from a loss of arginase-1, leading to impaired ureagenesis, hyperargininemia and neurological deficits Previously, we generated a tamoxifen-inducible arginase-1 deficient mouse model harboring a deletion of Arg1 exons 7 and 8 that leads to similar biochemical defects, along with a wasting phenotype and death within two weeks Here, we report a strategy utilizing the Clustered, Regularly Interspaced, Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system in conjunction with piggyBac technology to target and reincorporate exons 7 and 8 at the specific Arg1 locus in attempts to restore the function of arginase-1 in induced pluripotent stem cell (iPSC)-derived hepatocyte-like cells (iHLCs) and macrophages in vitro While successful gene targeted repair was achieved, minimal urea cycle function was observed in the targeted iHLCs compared to adult hepatocytes likely due to inadequate maturation of the cells On the other hand, iPSC-derived macrophages expressed substantial amounts of "repaired" arginase Our studies provide proof-of-concept for gene-editing at the Arg1 locus and highlight the challenges that lie ahead to restore sufficient liver-based urea cycle function in patients with urea cycle disorders
TL;DR: The observed changes in serum amino acids are compatible with urea cycle dysfunction, possibly due to reduced carbamoyl-phosphate synthase 1 (CPS1) activity.
Abstract: Administration of valproic acid (VPA) is complicated with approximately 0.9% of patients developing hyperammonemia, but the pathogenesis of this adverse effect remains to be clarified. The aim of the present study was to search for mechanisms associated with VPA-induced hyperammonemia in the light of changes in serum amino acids concentrations associated with the urea cycle of schizophrenic patients. Blood samples (10 mL) were obtained from 37 schizophrenic patients receiving VPA for the prevention of violent behaviors in the morning after overnight fast. Blood concentrations of ammonia, VPA, free carnitine, acyl-carnitine, and 40 amino acids including glutamate and citrulline were measured for each patient. Univariate and multivariate regression analyses were performed to identify amino acids or concomitantly administered drugs that were associated with variability in the blood concentrations of ammonia. The blood ammonia level was positively correlated with the serum glutamate concentration (r = 0.44, p < 0.01) but negatively correlated with glutamine (r = −0.41, p = 0.01), citrulline (r = −0.42, p = 0.01), and glycine concentrations (r = −0.54, p < 0.01). It was also revealed that the concomitant administration of the mood stabilizers (p = 0.04) risperidone (p = 0.03) and blonanserin (p < 0.01) was positively associated with the elevation of the blood ammonia level. We hypothisized that VPA would elevate the blood ammonia level of schizophrenic patients. The observed changes in serum amino acids are compatible with urea cycle dysfunction, possibly due to reduced carbamoyl-phosphate synthase 1 (CPS1) activity. We conclude that VPA should be prudently prescribed to schizophrenic patients, particularly those receiving mood stabilizers or certain antipsychotics.
TL;DR: A simple, robust and with no apparent risk method, offering a sensitive, minimal-invasive, and fast measurement of ureagenesis capacity using dried blood spots, which can be applied for the efficacy-testing of novel molecular therapies.
TL;DR: The results suggested that the SGT diets primarily influenced ascorbate metabolism and the urea cycle inUVB-irradiated mouse skin, alleviating deleterious UVB-induced skin wrinkles, epidermal thickening, and collagen-fiber destruction.
Abstract: While green tea is known to protect skin from ultraviolet (UV) light, underlying damage-repair mechanisms remain unclear The major objective of this study was to investigate, using multi-omics analysis, the metabolic mechanisms associated with the effects of a diet supplemented with green tea (SGT) in UVB-damaged mice Six to eight weeks old female Skh:HR-1 mice were randomly divided into three experimental groups ie, non-irradiated with control diet (NOR), UVB-irradiated with control diet (UND), and UVB-irradiated with SGT (UGD), and subjected to experimental conditions over 10 weeks The skin samples were analyzed by metabolomics, transcriptomics, and in silico modeling Our results revealed that SGT significantly alleviated UVB-induced metabolite alterations (aspartic acid, ornithine, ascorbic acid, ethanolamine, and C20:0-lysophosphatidylethanolamine) and gene expressions (keratin sulfate biosynthesis/degradation, fatty acid oxidation, and steroid metabolism) in the skin Among these changes, key metabolic pathways, including ascorbate metabolism and the urea cycle, were the major pathways mitigated through SGT diet among UGD group mice Additionally, SGT treatment also affected serum and hepatic lysophospholipid levels through attenuating and intensifying UVB-induced metabolic changes, respectively Our results suggested that the SGT diets primarily influenced ascorbate metabolism and the urea cycle in UVB-irradiated mouse skin, alleviating deleterious UVB-induced skin wrinkles, epidermal thickening, and collagen-fiber destruction
TL;DR: Activity of CPS I, OTC and ARG I/II enzymes in HepaRG monolayer cultures was considerably lower than in human control livers albeit an increase was achieved in HepARG-BAL cultures.
TL;DR: Ten neonates from eight families (finally) diagnosed with CPS1 deficiency at three tertiary metabolic centres are reported, and the laboratory findings were dominated by significantly elevated urinary 3-methylglutaconic acid levels which complicated the diagnostic process.
TL;DR: A 69-year-old man who presented at the local hospital with 3-day loss of appetite, early morning vomiting, and state of confusion went into a deep coma, and genetic analysis showed A208T mutation, which resulted in improvement of blood ammonia level.
Abstract: The urea cycle converts ammonia and produces urea. One form of urea cycle abnormality is ornithine transcarbamylase (OTC) deficiency. This hereditary disorder is associated with hyperammonemia. OTC deficiency commonly appears during neonatal and early childhood life and is rare in adults. We report a 69-year-old man who presented at the local hospital with 3-day loss of appetite, early morning vomiting, and state of confusion. Blood ammonia was 293 μg/dl. At 2–3 h after admission, the patient went into a deep coma. He was intubated and admitted immediately to the intensive care unit. Treatment, including sustained hemodialysis, failed to lower blood ammonia level. His grandchild died of OTC deficiency at 6 year of age. Computed tomography, magnetic resonance imaging and esophagogastroduodenoscopy showed no abnormalities. On admission to our hospital, he complained of vomiting and disturbance of consciousness, hyperammonemia, and normal anion gap. Genetic analysis showed A208T mutation. The deceased grandchild with OTC deficiency also had the same mutation. Long-term hemodialysis coupled with administration of l-arginine and lactulose resulted in improvement of blood ammonia level. Early diagnosis and treatment of adult-onset OTC deficiency are essential to avoid serious complications.
01 Oct 2017-Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation
TL;DR: Liver transplant should be an option for argininosuccinic aciduria patients to prevent further neurologic deterioration and improve the patient's quality of life, even in the absence of cirrhosis.
Abstract: Argininosuccinic aciduria is a urea cycle disorder caused by an argininosuccinate lyase enzyme deficiency that ends with nitrogen accumulation as ammonia. Argininosuccinic aciduria patients are at risk for long-term complications including poor neurocognitive outcome, hepatic disease, and systemic hypertension despite strict pharmacologic and dietary therapy. As the liver is the principle site of activity of the urea cycle, it is logical that a liver transplant should be an option, with careful patient selection, even in the absence of cirrhosis. We present 2 pediatric argininosuccinic aciduria patients who underwent a living-donor liver transplant from their mothers. After the liver transplant, the general well-being of the patients and their quality of life improved significantly. Liver transplant should be an option for argininosuccinic aciduria patients to prevent further neurologic deterioration and improve the patient's quality of life.
TL;DR: Results suggest that H. pylori infection causes various metabolic alterations at lesional sites, and these alterations might be linked to the crosstalk between H. pylori and the host leading to transition of disease conditions.
TL;DR: Findings indicate that exposure to seawater that held a donor conspecific for up to 48h (pre-conditioned seawater; PC-SW) induced a urea pulse within 7h in naïve Conspecifics compared to a pulse latency of 20h when exposed to seaw water alone, which suggests that urea pulsing may be linked to toadfish social behavior.
TL;DR: Metabolically based liver damage pathophysiology in patients with urea cycle disorders was studied in this paper, where the authors proposed a new hypothesis based on the hypothesis that liver damage is associated with UCD.
Abstract: Metabolically based liver damage pathophysiology in patients with urea cycle disorders - A new hypothesis
TL;DR: Glycerol phenyl butyrate is better tolerated than sodium phenylbutyrate and enables patients with urea cycle disorders to reach ammonia and glutamine targets and Maintenance of target ammonia levels allows better long-term control in patients with Urea cycle defects with reduced neurological sequelae.
Abstract: Introduction: Urea cycle disorders are rare inborn errors of metabolism resulting in the accumulation of ammonia. Over the last 3 decades, the use of alternative nitrogen excretion pathways has been exploited to improve survival and outcomes for urea cycle disorder patients.Areas covered: Early discovered nitrogen scavengers (sodium benzoate, phenylacetate, and phenylbutyrate) are effective in lowering ammonia. However, they have side effects and administration issues that can reduce compliance to therapy and limit optimal outcomes. Glycerol phenylbutyrate, a pro-drug of phenylbutyrate, was developed to improve therapy for patients with urea cycle disorders. Research with glycerol phenylbutyrate has produced the largest body of controlled study data in urea cycle disorder patients to date.Expert opinion: Glycerol phenylbutyrate is better tolerated than sodium phenylbutyrate and enables patients with urea cycle disorders to reach ammonia and glutamine targets. Maintenance of target ammonia levels a...
TL;DR: The present study result suggest that naringin modulates the expression of proteins involved in urea cycle pathway and suppresses theexpression of inflammatory markers and acts as a potential agent to treat condition in rats.