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Journal of Cataract and Refractive... Oct 2015
Topics: Anti-Inflammatory Agents, Non-Steroidal; Benzeneacetamides; Benzophenones; Bromobenzenes; Endophthalmitis; Humans; Ketorolac; Phacoemulsification; Phenylacetates; Postoperative Complications
PubMed: 26703275
DOI: 10.1016/j.jcrs.2015.10.056 -
Scientific Reports Oct 2017Urea cycle enzyme deficiency (UCED) patients with hyperammonemia are treated with sodium benzoate (SB) and sodium phenylacetate (SPA) to induce alternative pathways of...
Urea cycle enzyme deficiency (UCED) patients with hyperammonemia are treated with sodium benzoate (SB) and sodium phenylacetate (SPA) to induce alternative pathways of nitrogen excretion. The suggested guidelines supporting their use in the management of hyperammonemia are primarily based on non-analytic studies such as case reports and case series. Canine congenital portosystemic shunting (CPSS) is a naturally occurring model for hyperammonemia. Here, we performed cross-over, randomized, placebo-controlled studies in healthy dogs to assess safety and pharmacokinetics of SB and SPA (phase I). As follow-up safety and efficacy of SB was evaluated in CPSS-dogs with hyperammonemia (phase II). Pharmacokinetics of SB and SPA were comparable to those reported in humans. Treatment with SB and SPA was safe and both nitrogen scavengers were converted into their respective metabolites hippuric acid and phenylacetylglutamine or phenylacetylglycine, with a preference for phenylacetylglycine. In CPSS-dogs, treatment with SB resulted in the same effect on plasma ammonia as the control treatment (i.e. saline infusion) suggesting that the decrease is a result of volume expansion and/or forced diuresis rather than increased production of nitrogenous waste. Consequentially, treatment of hyperammonemia justifies additional/placebo-controlled trials in human medicine.
Topics: Animals; Dogs; Female; Hyperammonemia; Male; Nitrogen; Phenylacetates; Random Allocation; Saline Waters; Sodium Benzoate
PubMed: 29030642
DOI: 10.1038/s41598-017-12686-9 -
ACS Synthetic Biology Apr 2019Tropone is a seven-membered ring nonbenzenoid aromatic compound. It is the core structure of tropolonoids, which have various biological activities. In this study, a...
Tropone is a seven-membered ring nonbenzenoid aromatic compound. It is the core structure of tropolonoids, which have various biological activities. In this study, a hybrid tropone biosynthetic pathway was designed by connecting phenylacetic acid (PAA) degradation with its biosynthesis and reconstituted in Escherichia coli. To simplify pathway construction and optimization, the use of E. coli endogenous genes was maximized and only three exogenous genes were employed. The entire pathway was divided into four modules: the endogenous shikimate pathway module, the hybrid PAA biosynthetic module, the endogenous PAA catabolic module and the heterogeneous tropone biosynthetic module. Efficiency of the PAA catabolic module was enhanced using PAA consumption rate as the indicator. Then, a single point mutation was introduced to inactivate the ALDH domain of PaaZ and the carbon flow was redirected toward tropone synthesis. Assembly of the full pathway led to de novo tropone production with the best titer of 65.2 ± 1.4 mg/L in shake flask experiment. This study provides a potential alternative for sustainable production of tropone and its derivatives.
Topics: Aldehyde Dehydrogenase; Biosynthetic Pathways; Escherichia coli; Escherichia coli Proteins; Metabolic Engineering; Phenylacetates; Point Mutation; Shikimic Acid; Tropolone
PubMed: 30861343
DOI: 10.1021/acssynbio.9b00013 -
Molecular Genetics and Metabolism Nov 2023Medications that elicit an alternate pathway for nitrogen excretion such as oral sodium phenylbutyrate (NaPBA) and glycerol phenylbutyrate (GPB) and intravenous sodium...
Medications that elicit an alternate pathway for nitrogen excretion such as oral sodium phenylbutyrate (NaPBA) and glycerol phenylbutyrate (GPB) and intravenous sodium phenylacetate (NaPAA) are important for the management of urea cycle disorders (UCDs). Plasma concentrations of their primary metabolite, phenylacetate (PAA), as well as the ratio of PAA to phenylacetylglutamine (PAGN) are useful for guiding dosing and detecting toxicity. However, the frequency of toxic elevations of metabolites and associated clinical covariates is relatively unknown. A retrospective analysis was conducted on 1255 plasma phenylbutyrate metabolite measurements from 387 individuals. An additional analysis was also conducted on a subset of 68 individuals in whom detailed clinical information was available. In the course of these analyses, abnormally elevated plasma PAA and PAA:PAGN were identified in 39 individuals (4.15% of samples) and 42 individuals (4.30% of samples), respectively. Abnormally elevated PAA and PAA:PAGN values were more likely to occur in younger individuals and associate positively with dose of NAPBA and negatively with plasma glutamine and glycine levels. These results demonstrate that during routine clinical management, the majority of patients have PAA levels that are deemed safe. As age is negatively associated with PAA levels however, children undergoing treatment with NaPBA may need close monitoring of their phenylbutyrate metabolite levels.
Topics: Child; Humans; Phenylbutyrates; Retrospective Studies; Urea Cycle Disorders, Inborn
PubMed: 37717413
DOI: 10.1016/j.ymgme.2023.107699 -
PeerJ 2022T-37 can infect grapes and other fruit trees and cause root cancer. Given the pollution and damage of chemical agents to the environment, the use of biological control...
BACKGROUND
T-37 can infect grapes and other fruit trees and cause root cancer. Given the pollution and damage of chemical agents to the environment, the use of biological control has become an important area of focus. L2 is a beneficial biocontrol strain isolated and identified in the laboratory, which has a good antibacterial effect on a variety of plant pathogens. The antibacterial metabolites of L2 were separated and purified to obtain a bioactive compound phenylacetic acid (PAA).
METHODS
The potential antibacterial mechanism of PAA against T-37 strain was determined by relative conductivity, leakage of nucleic acids, proteins, and soluble total sugars, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and reactive oxygen species (ROS).
RESULTS
PAA showed good antibacterial activity against strain T-37 with IC of 0.8038 mg/mL. Our data suggested that after treatment with PAA, the relative conductivity, nucleic acid, protein, and total soluble sugar of T-37 were increased significantly compared with the chloramphenicol treatment group and the negative treatment group. The total protein synthesis of T-37 cells was inhibited, the consumption of phosphorus decreased with the increase of incubation time, and the content of ROS was significantly higher than that in the negative treatment group. Meanwhile, the activity of two key enzymes (MDH and SDH) involved in the tricarboxylic acid cycle (TCA cycle) decreased. In addition, T-37 cells were found to be damaged by scanning electron microscopy observation. Our results showed that PAA can destroy cell membrane integrity, damage cell structures, affect cell metabolism, and inhibit protein synthesis to exert an antibacterial effect.
CONCLUSIONS
We concluded that the mechanism of action of the PAA against strain T-37 might be described as PAA exerting antibacterial activity by affecting cell metabolism, inhibiting protein synthesis, and destroying cell membrane integrity and cell ultrastructure. Therefore, PAA has a promising application prospect in the prevention and treatment of root cancer disease caused by .
Topics: Agrobacterium tumefaciens; Bacillus megaterium; Reactive Oxygen Species; Solanum lycopersicum; Anti-Bacterial Agents; Phenylacetates
PubMed: 36389424
DOI: 10.7717/peerj.14304 -
Journal of Veterinary Pharmacology and... Nov 2022The aim of this study was to evaluate the pharmacokinetics (PK) of robenacoxib (RX), a COX-2 selective non-steroidal anti-inflammatory drug, in sheep after single...
The aim of this study was to evaluate the pharmacokinetics (PK) of robenacoxib (RX), a COX-2 selective non-steroidal anti-inflammatory drug, in sheep after single subcutaneous (SC), oral (PO), and intravenous (IV) administration. Five healthy female sheep underwent a three-phase parallel study design with a washout period of 4 weeks, in which sheep received a 4 mg/kg SC dose in phase 1, a 4 mg/kg PO administration in phase 2, and a 2 mg/kg IV administration in phase 3. Plasma RX concentrations were measured over a 48 h period for each treatment using HPLC coupled to a UV multiple wavelength detector, and the PK parameters were estimated using a non-compartmental method. Following IV administration, terminal elimination half-life, volume of distribution at steady state, and total clearance were 2.64 h, 0.077 L/kg, and 0.056 L/h kg, respectively. The mean peak plasma concentrations following SC and PO administrations were 7.04 and 3.01 μg/mL, respectively. The mean bioavailability following SC and PO administrations were 45.98% and 16.58%, respectively. The SC route may be proposed for use in sheep. However, the multi-dose and pharmacodynamic studies are necessary to establish more accurately its safety and efficacy in sheep.
Topics: Female; Sheep; Animals; Area Under Curve; Phenylacetates; Diphenylamine; Administration, Intravenous; Administration, Oral; Biological Availability; Half-Life
PubMed: 35899473
DOI: 10.1111/jvp.13089 -
Arthritis & Rheumatology (Hoboken, N.J.) Aug 2016
Topics: Acetamides; Phenylacetates
PubMed: 26990165
DOI: 10.1002/art.39687 -
Food Research International (Ottawa,... Nov 2022Poultry products are an essential animal source of protein for humans. Many factors could destroy the balance of the poultry production chain and cause an overstock of...
Poultry products are an essential animal source of protein for humans. Many factors could destroy the balance of the poultry production chain and cause an overstock of products, which need to be stored in the frozen storage warehouse for a long time. The long-term frozen storage may affect the quality of meat products. In this study, the changes of small molecular substances were revealed in duck meat during long-term storage using non-targeted metabolomics. The results showed that compared with fresh meat, even if the meat is stored under frozen storage conditions, the number of differential metabolites of frozen storage meat continues to increase with the prolongation of storage time, indicating that the meat composition has changed significantly with the storage time increased. With the increase in storage time, the nitrogen-containing small molecular compounds in duck meat increased (carnosine and anserine, aspartic acid, and tyrosine, 1H-indole-3-acetamide, 2-Hydroxyphenethylamine, 2-Naphylamine, allocystathionine, and O-phosphoethanolamine), the nucleotides decomposition process strengthened (IMP and AMP, GMP and UMP), and the content of organic acid increased (5-hydroxy indole acetic acid, 5-hydroxypentanoic acid and phenylacetate, taurine) and carbohydrate (1-O-sinapoyl-beta-d-glucose, 4-O-beta-d-glucopyranosyl-d-mannose, and alpha-d-glucose). These small molecular substances can be used as biomarkers to detect long-term stored duck meat deterioration. KEGG enrichment analysis showed that protein catabolism, nucleotide catabolism, fat decomposition and oxidation, and carbohydrate decomposition were the main metabolic processes of meat deterioration during the long-term storage of duck meat. In addition, Non-target metabolome technology is a powerful tool to reveal the meat deterioration process during long-term storage systematically. This study provided a reference for optimizing domestic poultry meat storage methods and ensuring food safety.
Topics: Animals; Humans; 2-Hydroxyphenethylamine; Adenosine Monophosphate; Anserine; Aspartic Acid; Carbohydrates; Carnosine; Ducks; Glucose; Meat; Nitrogen; Phenylacetates; Taurine; Tyrosine; Uridine Monophosphate
PubMed: 36192983
DOI: 10.1016/j.foodres.2022.111859 -
Nature Chemical Biology May 2018Microbial toluene biosynthesis was reported in anoxic lake sediments more than three decades ago, but the enzyme catalyzing this biochemically challenging reaction has...
Microbial toluene biosynthesis was reported in anoxic lake sediments more than three decades ago, but the enzyme catalyzing this biochemically challenging reaction has never been identified. Here we report the toluene-producing enzyme PhdB, a glycyl radical enzyme of bacterial origin that catalyzes phenylacetate decarboxylation, and its cognate activating enzyme PhdA, a radical S-adenosylmethionine enzyme, discovered in two distinct anoxic microbial communities that produce toluene. The unconventional process of enzyme discovery from a complex microbial community (>300,000 genes), rather than from a microbial isolate, involved metagenomics- and metaproteomics-enabled biochemistry, as well as in vitro confirmation of activity with recombinant enzymes. This work expands the known catalytic range of glycyl radical enzymes (only seven reaction types had been characterized previously) and aromatic-hydrocarbon-producing enzymes, and will enable first-time biochemical synthesis of an aromatic fuel hydrocarbon from renewable resources, such as lignocellulosic biomass, rather than from petroleum.
Topics: Acidobacteria; Anaerobiosis; Bacteria; Biomass; Carboxy-Lyases; Catalysis; Genes, Bacterial; Geologic Sediments; Lakes; Lignin; Likelihood Functions; Metagenomics; Microbiota; Phenylacetates; Phylogeny; Proteomics; Recombinant Proteins; Sewage; Toluene
PubMed: 29556105
DOI: 10.1038/s41589-018-0017-4 -
Food and Chemical Toxicology : An... May 2019
Review
Topics: Animals; Ecotoxicology; Endpoint Determination; Environmental Pollutants; Humans; Odorants; Perfume; Phenylacetates; Risk Assessment; Salmonella typhimurium
PubMed: 30605701
DOI: 10.1016/j.fct.2018.12.049