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Amino Acids Jul 2022A considerable number of studies have reported that maternal protein restriction may disturb fetal growth and organ development due to a lower availability of amino...
Effects of maternal branched-chain amino acid and alanine supplementation on growth and biomarkers of protein metabolism in dams fed a low-protein diet and their offspring.
A considerable number of studies have reported that maternal protein restriction may disturb fetal growth and organ development due to a lower availability of amino acids. Leucine, one of branched-chain amino acid (BCAA) promotes protein synthesis through mechanistic target of rapamycin signaling. Here, we investigated the effects of BCAA supplementation in the dams fed a low-protein diet on serum and hepatic biochemical parameters of protein metabolism of dams and their offspring. Female ICR mice were fed a control (20% casein), a low-protein (10% casein), a low-protein with 2% BCAAs or a low-protein with 2% alanine diet for 2 weeks before mating and then throughout pregnancy and lactation. Alanine was used as an amino nitrogen control for the BCAA. Dams and their male offspring were sacrificed at postnatal day 21. There were no changes in body weight and fat mass in low-protein fed dams; however, BCAA supplementation significantly increased fat mass and serum leptin levels. Low-protein diet consumption reduced maternal protein synthesis based on biochemical analysis of serum albumin and hepatic protein levels and immunoblotting of S6 protein, which were increased by BCAA and alanine supplementation. Offspring from dams fed a low-protein diet exhibited lower body and organ weights. Body weight and hepatic protein levels of the offspring were increased by alanine supplementation. However, the decreased serum biochemical parameters, including glucose, triglyceride, total protein and albumin levels in the low-protein offspring group were not changed in response to BCAA or alanine supplementation. A reduced density of the hepatic vessel system in the offspring from dams fed a low-protein diet was restored in the offspring from dams fed either BCAA and alanine-supplemented diet. These results suggest that supplementation of amino nitrogen per se may be responsible for inducing hepatic protein synthesis in the dams fed a low-protein diet and alleviating the distorted growth and liver development of their offspring.
Topics: Alanine; Amino Acids, Branched-Chain; Animals; Biomarkers; Body Weight; Caseins; Diet, High-Fat; Diet, Protein-Restricted; Dietary Supplements; Female; Liver; Male; Mice; Mice, Inbred ICR; Pregnancy
PubMed: 35353249
DOI: 10.1007/s00726-022-03157-1 -
Clinical and Translational Science Apr 2022
Topics: Adenosine Monophosphate; Alanine; Cardiovascular Diseases; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmacovigilance; Product Surveillance, Postmarketing
PubMed: 35303401
DOI: 10.1111/cts.13261 -
European Review For Medical and... Jul 2021The purpose of this narrative review is to discuss the available information regarding the currently utilized COVID-19 therapies (and the evidence level supporting them)... (Review)
Review
OBJECTIVE
The purpose of this narrative review is to discuss the available information regarding the currently utilized COVID-19 therapies (and the evidence level supporting them) and opioids for chronic pain with a focus on warnings of potential interactions between these two therapeutic approaches.
MATERIALS AND METHODS
Papers were retrieved from a PubMed search, using different combinations of keywords [e.g., pain treatment AND COVID-19 AND drug-drug interaction (DDI)], without limitations in terms of publication date and language.
RESULTS
Remdesivir is an inhibitor of CYP3A4 and may increase the plasma concentration of CYP3A4 substrates (e.g., fentanyl). Dexamethasone is an inducer of CYP3A4 and glycoprotein P, thus coadministration with drugs metabolized by this isoform will lead to their increased clearance. Dexamethasone may cause hypokalemia, thus potentiating the risk of ventricular arrhythmias if it is given with opioids able to prolong the QT interval, such as oxycodone and methadone. Finally, the existing differences among opioids with regard to their impact on immune responses should also be taken into account with only tapentadol and hydromorphone appearing neutral on both cytokine production and immune parameters.
CONCLUSIONS
Clinicians should keep in mind the frequent DDIs with drugs extensively metabolized by the CYP450 system and prefer opioids undergoing a limited hepatic metabolism. Identification and management of DDIs and dissemination of the related knowledge should be a major goal in the delivery of chronic care to ensure optimized patient outcomes and facilitate updating recommendations for COVID-19 therapy in frail populations, namely comorbid, poly-medicated patients or individuals suffering from substance use disorder.
Topics: Adenosine Monophosphate; Alanine; Analgesics, Opioid; Anti-Inflammatory Agents; Antiviral Agents; Chronic Pain; Dexamethasone; Drug Interactions; Humans; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34337735
DOI: 10.26355/eurrev_202107_26399 -
The American Journal of Nursing Jan 2021According to this study: The antiviral remdesivir is superior to placebo in the treatment of patients hospitalized with COVID-19.A variety of therapeutic approaches are... (Randomized Controlled Trial)
Randomized Controlled Trial
According to this study: The antiviral remdesivir is superior to placebo in the treatment of patients hospitalized with COVID-19.A variety of therapeutic approaches are needed to continue to improve outcomes in COVID-19 patients.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Double-Blind Method; Female; Humans; Male; Middle Aged; COVID-19 Drug Treatment
PubMed: 33350698
DOI: 10.1097/01.NAJ.0000731668.01845.8c -
The Lancet. Infectious Diseases Dec 2021
Topics: Adenosine Monophosphate; Alanine; Humans
PubMed: 34838223
DOI: 10.1016/S1473-3099(21)00693-9 -
CMAJ : Canadian Medical Association... Jan 2021
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Chemical and Drug Induced Liver Injury; Critical Care; Drug Hypersensitivity; Humans; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 33408097
DOI: 10.1503/cmaj.202505 -
The Lancet. Infectious Diseases Dec 2021
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Humans; Randomized Controlled Trials as Topic; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 34838222
DOI: 10.1016/S1473-3099(21)00695-2 -
Journal of Biomolecular Structure &... Nov 2022Theoretical calculations have been performed to study the structures of L-alanine and its zwitterionic form in the gas phase and in solution. The energies and the...
Theoretical calculations have been performed to study the structures of L-alanine and its zwitterionic form in the gas phase and in solution. The energies and the vibrational frequencies of the L-alanine in both neutral and zwitterionic form have been calculated using HF, MP2, CCSD and density functional theory (DFT) B3LYP hybrid exchange correlation functional with different basis sets. The conductor-like solvation model of the polarizable continuum model (CPCM) has been used to compute energies, geometric structures and harmonic frequencies in solution for the L-alanine and its zwitterionic form. We have shown how the choice of the basis sets is important to improve the accuracy of the model theory. We have also observed significant changes in frequencies when L-alanine and its zwitterionic form are in solution. Classical Molecular dynamic simulation has also been conducted to get an idea about the organization of water molecules around alanine's hydrophilic sites. The results indicated that water molecules seems to prefer keeping a structure formed by hydrogen bonded water-water molecules around the COO site rather than forming hydrogen bond.Communicated by Ramaswamy H. Sarma.
Topics: Alanine; Hydrogen; Models, Molecular; Quantum Theory; Thermodynamics; Water
PubMed: 33970793
DOI: 10.1080/07391102.2021.1918580 -
Mini Reviews in Medicinal Chemistry 2021Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus strain and the causative agent of COVID-19 was emerged in Wuhan, China, in December... (Review)
Review
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus strain and the causative agent of COVID-19 was emerged in Wuhan, China, in December 2019 [1]. This pandemic situation and magnitude of suffering have led to global effort to find out effective measures for discovery of new specific drugs and vaccines to combat this deadly disease. In addition to many initiatives to develop vaccines for protective immunity against SARS-CoV-2, some of which are at various stages of clinical trials, researchers worldwide are currently using available conventional therapeutic drugs with the potential to combat the disease effectively in other viral infections and it is believed that these antiviral drugs could act as a promising immediate alternative. Remdesivir (RDV), a broad-spectrum anti-viral agent, initially developed for the treatment of Ebola virus (EBOV) and known to showed promising efficiency in in vitro and in vivo studies against SARS and MERS coronaviruses, is now being investigated against SARS-CoV-2. On May 1, 2020, The U.S. Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) for RDV to treat COVID- 19 patients [2]. A number of multicentre clinical trials are on-going to check the safety and efficacy of RDV for the treatment of COVID-19. Results of published double blind, and placebo-controlled trial on RDV against SARS-CoV-2, showed that RDV administration led to faster clinical improvement in severe COVID-19 patients compared to placebo. This review highlights the available knowledge about RDV as a therapeutic drug for coronaviruses and its preclinical and clinical trials against COVID-19.
Topics: Adenosine Monophosphate; Alanine; Animals; Antiviral Agents; COVID-19; Humans; Randomized Controlled Trials as Topic; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 33596800
DOI: 10.2174/1389557521666210217093004 -
Analytical Chemistry Jan 2024Lanthipeptides make up a large group of natural products that belong to the ribosomally synthesized and post-translationally modified peptides (RiPPs). Lanthipeptides...
Lanthipeptides make up a large group of natural products that belong to the ribosomally synthesized and post-translationally modified peptides (RiPPs). Lanthipeptides contain lanthionine and methyllanthionine bis-amino acids that have varying stereochemistry. The stereochemistry of new lanthipeptides is often not determined because current methods require equipment that is not standard in most laboratories. In this study, we developed a facile, efficient, and user-friendly method for detecting lanthipeptide stereochemistry, utilizing advanced Marfey's analysis with detection by liquid chromatography coupled with mass spectrometry (LC-MS). Under optimized conditions, 0.05 mg of peptide is sufficient to characterize the stereochemistry of five (methyl)lanthionines of different stereochemistry using a simple liquid chromatography setup, which is a much lower detection limit than current methods. In addition, we describe methods to readily access standards of the three different methyllanthionine stereoisomers and two different lanthionine stereoisomers that have been reported in known lanthipeptides. The developed workflow uses a commonly used nonchiral column system and offers a scalable platform to assist antimicrobial discovery. We illustrate its utility with an example of a lanthipeptide discovered by genome mining.
Topics: Peptides; Sulfides; Alanine; Chromatography, Liquid
PubMed: 38232355
DOI: 10.1021/acs.analchem.3c04958