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Nature Reviews. Nephrology Aug 2020Hyperammonaemia in children can lead to grave consequences in the form of cerebral oedema, severe neurological impairment and even death. In infants and children, common... (Review)
Review
Hyperammonaemia in children can lead to grave consequences in the form of cerebral oedema, severe neurological impairment and even death. In infants and children, common causes of hyperammonaemia include urea cycle disorders or organic acidaemias. Few studies have assessed the role of extracorporeal therapies in the management of hyperammonaemia in neonates and children. Moreover, consensus guidelines are lacking for the use of non-kidney replacement therapy (NKRT) and kidney replacement therapies (KRTs, including peritoneal dialysis, continuous KRT, haemodialysis and hybrid therapy) to manage hyperammonaemia in neonates and children. Prompt treatment with KRT and/or NKRT, the choice of which depends on the ammonia concentrations and presenting symptoms of the patient, is crucial. This expert Consensus Statement presents recommendations for the management of hyperammonaemia requiring KRT in paediatric populations. Additional studies are required to strengthen these recommendations.
Topics: Arginine; Carnitine; Child; Child, Preschool; Continuous Renal Replacement Therapy; Delphi Technique; Diet, Protein-Restricted; Humans; Hybrid Renal Replacement Therapy; Hyperammonemia; Infant; Infant, Newborn; Parenteral Nutrition; Peritoneal Dialysis; Phenylacetates; Phenylbutyrates; Practice Guidelines as Topic; Renal Dialysis; Sodium Benzoate; Urea Cycle Disorders, Inborn; Vitamin B Complex
PubMed: 32269302
DOI: 10.1038/s41581-020-0267-8 -
Drugs May 2015Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) of the phenylacetic acid class with anti-inflammatory, analgesic, and antipyretic properties. Contrary to the... (Review)
Review
Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) of the phenylacetic acid class with anti-inflammatory, analgesic, and antipyretic properties. Contrary to the action of many traditional NSAIDs, diclofenac inhibits cyclooxygenase (COX)-2 enzyme with greater potency than it does COX-1. Similar to other NSAIDs, diclofenac is associated with serious dose-dependent gastrointestinal, cardiovascular, and renal adverse effects. Since its introduction in 1973, a number of different diclofenac-containing drug products have been developed with the goal of improving efficacy, tolerability, and patient convenience. Delayed- and extended-release forms of diclofenac sodium were initially developed with the goal of improving the safety profile of diclofenac and providing convenient, once-daily dosing for the treatment of patients with chronic pain. New drug products consisting of diclofenac potassium salt were associated with faster absorption and rapid onset of pain relief. These include diclofenac potassium immediate-release tablets, diclofenac potassium liquid-filled soft gel capsules, and diclofenac potassium powder for oral solution. The advent of topical formulations of diclofenac enabled local treatment of pain and inflammation while minimizing systemic absorption of diclofenac. SoluMatrix diclofenac, consisting of submicron particles of diclofenac free acid and a proprietary combination of excipients, was developed to provide analgesic efficacy at reduced doses associated with lower systemic absorption. This review illustrates how pharmaceutical technology has been used to modify the pharmacokinetic properties of diclofenac, leading to the creation of novel drug products with improved clinical utility.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Chemistry, Pharmaceutical; Cyclooxygenase Inhibitors; Delayed-Action Preparations; Diclofenac; Dose-Response Relationship, Drug; Humans; Technology, Pharmaceutical
PubMed: 25963327
DOI: 10.1007/s40265-015-0392-z -
Molecules (Basel, Switzerland) Sep 2023Catechols have important applications in the pharmaceutical, food, cosmetic, and functional material industries. 4-hydroxyphenylacetate-3-hydroxylase (4HPA3H), a... (Review)
Review
Catechols have important applications in the pharmaceutical, food, cosmetic, and functional material industries. 4-hydroxyphenylacetate-3-hydroxylase (4HPA3H), a two-component enzyme system comprising HpaB (monooxygenase) and HpaC (FAD oxidoreductase), demonstrates significant potential for catechol production because it can be easily expressed, is highly active, and exhibits -hydroxylation activity toward a broad spectrum of phenol substrates. HpaB determines the -hydroxylation efficiency and substrate spectrum of the enzyme; therefore, studying its structure-activity relationship, improving its properties, and developing a robust HpaB-conducting system are of significance and value; indeed, considerable efforts have been made in these areas in recent decades. Here, we review the classification, molecular structure, catalytic mechanism, primary efforts in protein engineering, and industrial applications of HpaB in catechol synthesis. Current trends in the further investigation of HpaB are also discussed.
Topics: Mixed Function Oxygenases; Catechols; Phenylacetates
PubMed: 37764475
DOI: 10.3390/molecules28186699 -
Endocrine Oct 2019Several metabolic products that derive from L-thyroxine (T4) and 3,3'5-L-triiodothyronine (T3), the main thyroid hormones secreted by the thyroid gland, possess biologic... (Review)
Review
Several metabolic products that derive from L-thyroxine (T4) and 3,3'5-L-triiodothyronine (T3), the main thyroid hormones secreted by the thyroid gland, possess biologic activities. Among these metabolites or derivatives showing physiological actions some have received greater attention: diiodothyronines, iodothyronamines, acetic acid analogues. It is known that increased thyroid hormone (T3 and T4) levels can improve serum lipid profiles and reduce body fat. These positive effects are, however, counterbalanced by adverse effects on the heart, muscle and bone, limiting their use. In addition to the naturally occurring metabolites, thyroid hormone analogues have been developed that either have selective effects on specific tissues or bind selectively to thyroid hormone receptor (TR) isoform. Among these GC-1, KB141, KB2115, and DITPA were deeply investigated and displayed promising therapeutic results in the potential treatment of conditions such as dyslipidemias and obesity. In this review, we summarize the current knowledge of metabolites and analogues of T4 and T3 with reference to their possible clinical application in the treatment of human diseases.
Topics: Acetates; Anilides; Animals; Diiodothyronines; Humans; Phenols; Phenyl Ethers; Phenylacetates; Propionates; Thyroid Hormones
PubMed: 31359245
DOI: 10.1007/s12020-019-02025-5 -
Phytotherapy Research : PTR Jun 2021Lichens are symbiotic organisms which are composed fungi and algae and/or cyanobacteria. They produce a variety of characteristic secondary metabolites. Such substances... (Review)
Review
Lichens are symbiotic organisms which are composed fungi and algae and/or cyanobacteria. They produce a variety of characteristic secondary metabolites. Such substances have various biological properties including antimicrobial, antiviral, and antitumor activities. Angiogenesis, the growth of new vessels from pre-existing vessels, contributes to numerous diseases including cancer, arthritis, atherosclerosis, infectious, and immune disorders. Antiangiogenic therapy is a promising approach for the treatment of such diseases by inhibiting the new vessel formation. Technological advances have led to the development of various antiangiogenic agents and have made possible antiangiogenic therapy in many diseases associated with angiogenesis. Some lichens and their metabolites are used in the drug industry, but many have not yet been tested for their antiangiogenic effects. The cytotoxic and angiogenic capacities of lichen-derived small molecules have been demonstrated in vivo and in vitro experiments. Therefore, some of them may be used as antiangiogenic agents in the future. The secondary compounds of lichen whose antiangiogenic effect has been studied in the literature are usnic acid, barbatolic acid, vulpinic acid, olivetoric acid, emodin, secalonic acid D, and parietin. In this article, we review the antiangiogenic effects and cellular targets of these lichen-derived metabolites.
Topics: Angiogenesis Inhibitors; Anti-Infective Agents; Benzofurans; Biological Products; Cyanobacteria; Emodin; Fungi; Furans; Humans; Lichens; Phenylacetates; Salicylates; Xanthones
PubMed: 33587324
DOI: 10.1002/ptr.7023 -
Clinical & Experimental Optometry Apr 2022The role of topical non-steroidal anti-inflammatory drugs (NSAIDs) in routine cataract surgery has been established since decades. Topical NSAIDs have been shown to... (Review)
Review
The role of topical non-steroidal anti-inflammatory drugs (NSAIDs) in routine cataract surgery has been established since decades. Topical NSAIDs have been shown to reduce postoperative ocular inflammation and pain, preserve intraoperative mydriasis, and reduce the risk of postoperative cystoid macular oedema, whilst carrying a very low side-effect profile. Nepafenac is one of the currently available topical NSAIDs. The studies have shown that is has a high ocular penetration, allowing for potentially better results than other NSAIDs. This review gathers the current literature on the role of nepafenac in cataract surgery aiming to help surgeons maximise the benefits of its use to achieve improved surgical outcomes.
Topics: Benzeneacetamides; Cataract; Cataract Extraction; Humans; Phenylacetates; Postoperative Complications
PubMed: 34210237
DOI: 10.1080/08164622.2021.1945412 -
Plant & Cell Physiology Feb 2019Plant hormone biology is an ever-evolving field and as such, novel avenues of research must always be sought. Technological and theoretical advancement can also allow... (Review)
Review
Plant hormone biology is an ever-evolving field and as such, novel avenues of research must always be sought. Technological and theoretical advancement can also allow for previously dismissed research to yield equally interesting insights into processes now that they are better understood. The auxin phenylacetic acid (PAA) is an excellent example of this. PAA is a plant auxin that also possesses substantial antimicrobial activity. It has a broad distribution and has been studied in bacteria, fungi, algae and land plants. Research on this compound in plants was prominent in the 1980s, where its bioactivity and broad distribution were frequently examined. Unfortunately, due to the strong interest in the quintessential auxin, indole-3-acetic acid (IAA), research on PAA quickly petered out. Recently, several groups have resumed investigations on this hormone in plants, yet, little is known about PAA biology and its physiological role is unclear. PAA biosynthesis from the amino acid Phe invites direct comparisons with previously studied IAA biosynthesis pathways, and recent work has shown that PAA metabolism and signaling appears to be similar to that of IAA. However, given the large gap between previous work and recent investigations, a historical review of this auxin is required to renew our understanding of PAA. Here, previous work on PAA is reassessed in light of recent research in plants and serves as a synthesis of current knowledge on PAA biology.
Topics: Botany; History, 20th Century; History, 21st Century; Phenylacetates; Plant Growth Regulators; Plant Physiological Phenomena; Plants
PubMed: 30649529
DOI: 10.1093/pcp/pcz004 -
Retina (Philadelphia, Pa.) Jan 2015
Topics: Anti-Inflammatory Agents, Non-Steroidal; Benzeneacetamides; Eye Pain; Female; Humans; Intravitreal Injections; Male; Phenylacetates
PubMed: 25473790
DOI: 10.1097/IAE.0000000000000424 -
ChemSusChem May 2022Natural phenethyl acetate (PEA), phenylacetic acid (PAA), ethyl phenylacetate (Et-PA), and phenethyl phenylacetate (PE-PA) are highly desirable aroma chemicals, but with...
Natural phenethyl acetate (PEA), phenylacetic acid (PAA), ethyl phenylacetate (Et-PA), and phenethyl phenylacetate (PE-PA) are highly desirable aroma chemicals, but with limited availability and high price. Here, green, sustainable, and efficient bioproduction of these chemicals as natural products from renewable feedstocks was developed. PEA and PAA were synthesized from l-phenylalanine (l-Phe) via novel six- and five-enzyme cascades, respectively. Whole-cell-based cascade biotransformation of 100 mm l-Phe in a two-phase system (aqueous/organic: 1 : 0.5 v/v) containing ethyl oleate or biodiesel as green solvent gave 13.6 g L PEA (83.1 % conv.) and 11.6 g L PAA (87.1 % conv.), respectively. Coupled fermentation and biotransformation approach produced 10.4 g L PEA and 9.2 g L PAA from glucose or glycerol, respectively. The biosynthesized PAA was converted to natural Et-PA and PE-PA by esterification using lipases with ethanol or 2-phenylethanol derived from sugar, affording 2.7 g L Et-PA (83.1 % conv.) and 4.6 g L PE-PA (96.3 % conv.), respectively.
Topics: Acetates; Fermentation; Phenylacetates; Phenylalanine
PubMed: 35068056
DOI: 10.1002/cssc.202102645 -
Drug Metabolism and Pharmacokinetics Feb 2023TAK-123, a combination of sodium phenylacetate (NaPA) and sodium benzoate (NaBZ), is an intravenously administered drug developed for the treatment of acute...
TAK-123, a combination of sodium phenylacetate (NaPA) and sodium benzoate (NaBZ), is an intravenously administered drug developed for the treatment of acute hyperammonemia in infants, children, and adults with urea cycle enzyme deficiencies. The aim of the current study was to evaluate the pharmacokinetics, safety, and tolerability after intravenous infusion of TAK-123 in Japanese healthy adult volunteers. Ten volunteers received a 3.75 g/m loading dose of TAK-123 over a period of 1.5 h followed by a maintenance infusion of the same dose over 24 h. Phenylacetate (PA) and benzoate (BZ) and their respective metabolites, phenylacetylglutamine (PAG) and hippurate (HIP) were measured over a 24-h period using a high-performance liquid chromatography/tandem mass spectrometry method. Non-compartmental analysis was performed using WinNonlin® Professional. During the loading dose, plasma levels of both PA and BZ peaked at 1.5 h. Plasma PA levels plateaued and were maintained up to 6.5 h, whereas plasma BZ levels declined rapidly after switching to maintenance infusion. Urinary excretion ratios of PAG and HIP at 48 h after the administration were 99.3% and 104%, respectively, suggesting that almost all NaPA and NaBZ were metabolized and excreted into urine. Overall, TAK-123 was well-tolerated in healthy Japanese adults.
Topics: Adult; Child; Infant; Humans; Sodium Benzoate; East Asian People; Hyperammonemia; Phenylacetates; Benzoates; Healthy Volunteers
PubMed: 36529053
DOI: 10.1016/j.dmpk.2022.100474