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Journal of Perianesthesia Nursing :... Jun 2022
Topics: Alanine; Humans; Perioperative Nursing; Silicate Cement; Societies, Nursing
PubMed: 35667813
DOI: 10.1016/j.jopan.2022.02.007 -
Journal of Food Biochemistry Jan 2021Diabetes is a metabolic disorder whose complications are among the leading cause of death. In this study, the antidiabetic effect of L-alanine was tested in...
Diabetes is a metabolic disorder whose complications are among the leading cause of death. In this study, the antidiabetic effect of L-alanine was tested in alloxan-induced diabetic rats. Thirty-five male albino Wistar rats were divided into five groups viz; Group I and II: nondiabetic and diabetic controls respectively; Group III and IV: 150 and 300 mg/kg b.w. L-alanine treated, respectively; Group V: glibenclamide (0.5 mg/kg b.w.) treated. Weight and blood glucose were monitored during the study, while liver and kidney functions, lipid profile, and antioxidant markers were examined at the end of the study. The outcomes indicate that 300 mg/kg L-alanine resulted to a significant decrease (p < .05) in weight and blood glucose. L-alanine restored tissue antioxidants, kidney, and liver functions by improving important parameters. Histopathological studies showed the potential of L-alanine in regeneration of the islets of Langerhans. These findings suggest that L-alanine has an alleviating effect on alloxan-induced diabetes. PRACTICAL APPLICATIONS: Several medicinal plants have been tested for their antidiabetic potentials, however, the isolation of the active compounds from these plants for medicinal use is often challenging. Here, we present data that suggests the potential use of a pure and harmless amino acid compound (L-alanine) for the management of diabetes. L-alanine is readily available, cheap and can also be found in many foods we eat. Therefore, L-alanine may be taken by diabetic patients as a food supplement for the treatment/management of diabetes or taken as part of foods rich in the amino acid such as meat, poultry, fish, eggs, and dairy products.
Topics: Alanine; Alloxan; Animals; Blood Glucose; Diabetes Mellitus, Experimental; Dietary Supplements; Humans; Male; Plant Extracts; Rats; Rats, Wistar
PubMed: 33346923
DOI: 10.1111/jfbc.13590 -
Antiviral Research Aug 2023Remdesivir is a nucleotide prodrug with preclinical efficacy against lethal Nipah virus infection in African green monkeys when administered 1 day post inoculation (dpi)...
Remdesivir is a nucleotide prodrug with preclinical efficacy against lethal Nipah virus infection in African green monkeys when administered 1 day post inoculation (dpi) (Lo et al., 2019). Here, we determined whether remdesivir treatment was still effective when treatment administration initiation was delayed until 3 dpi. Three groups of six African green monkeys were inoculated with a lethal dose of Nipah virus, genotype Bangladesh. On 3 dpi, one group received a loading dose of 10 mg/kg remdesivir followed by daily dosing with 5 mg/kg for 11 days, one group received 10 mg/kg on 12 consecutive days, and the remaining group received an equivalent volume of vehicle solution. Remdesivir treatment initiation on 3 dpi provided partial protection from severe Nipah virus disease that was dose dependent, with 67% of animals in the high dose group surviving the challenge. However, remdesivir treatment did not prevent clinical disease, and surviving animals showed histologic lesions in the brain. Thus, early administration seems critical for effective remdesivir treatment during Nipah virus infection.
Topics: Animals; Chlorocebus aethiops; Henipavirus Infections; Brain; Adenosine Monophosphate; Alanine; Nipah Virus
PubMed: 37356729
DOI: 10.1016/j.antiviral.2023.105658 -
Pharmacology 2021The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiology of COVID-19 pandemic, resulted in significant harm to the affected countries in every... (Review)
Review
BACKGROUND
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiology of COVID-19 pandemic, resulted in significant harm to the affected countries in every aspect of life. The virus infected over 139 million patients and resulted in over 2.9 million deaths until April 16, 2021. New variants of this virus were identified that spread rapidly worldwide.
SUMMARY
Remdesivir, a prodrug of adenosine nucleotide analog, is an antiviral with a broad spectrum of activity that was tested on SARS and Middle East respiratory syndrome infections. In vitro studies conducted on SARS-CoV-2 revealed that remdesivir inhibited viral replication with high selectivity index in cell cultures. In vivo studies showed that remdesivir reduced viral load in bronchoalveolar lavage fluid and attenuated pulmonary infiltrates in infected animals. Further, remdesivir showed promising results in terms of clinical improvement, shortening the recovery time, mortality rate, and the duration of oxygen need, despite that some clinical trials did not reveal significant effect on remdesivir use. Several studies showed positive results of remdesivir against the new variants. Key Messages: Remdesivir showed a promising beneficial effect against new variants of SARS-CoV-2, but more clinical evidence is needed to confirm this effect.
Topics: Adenosine Monophosphate; Alanine; Animals; Antiviral Agents; COVID-19; Humans; Pandemics; Randomized Controlled Trials as Topic; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34515227
DOI: 10.1159/000518440 -
Organic & Biomolecular Chemistry Apr 2022Thiols are a functional group commonly used for selective reactions in a biochemical setting because of their high nucleophilicity. Phosphorus nucleophiles can undergo...
Thiols are a functional group commonly used for selective reactions in a biochemical setting because of their high nucleophilicity. Phosphorus nucleophiles can undergo some similar reactions to thiols, but remain underexploited in this setting. In this work we show that phosphine nucleophiles react cleanly and quickly with a dehydroalanine electrophile, itself generated from cysteine, to give a stable adduct in a peptide context. NMR reveals the product to be a phosphonium ion and indicates some backbone conformational constraint, possibly arising from transient carbonyl coordination. The reaction proceeded quickly, with a pseudo-first order rate constant of 0.126 min at 1 mM peptide (80% conversion in 10 min), and with no detectable side products on the peptide. A broad peptide sequence scope and water-soluble phosphines with alkyl as well as aromatic groups were all shown to react efficiently. Phosphine addition proved to be efficient on nisin as a model Dha-containing biologically-derived peptide and on an mRNA-displayed peptide, as well as on TCEP-modified agarose for peptide capture from solution. This reaction thus presents a promising approach for modification of peptides for cargo attachment or altered physical properties in peptide discovery.
Topics: Alanine; Amino Acid Sequence; Phosphines; Sulfhydryl Compounds
PubMed: 35353113
DOI: 10.1039/d2ob00410k -
Clinical Pharmacokinetics May 2021Remdesivir (RDV, Veklury) is a once-daily, nucleoside ribonucleic acid polymerase inhibitor of severe acute respiratory syndrome coronavirus 2 replication. Remdesivir... (Review)
Review
Remdesivir (RDV, Veklury) is a once-daily, nucleoside ribonucleic acid polymerase inhibitor of severe acute respiratory syndrome coronavirus 2 replication. Remdesivir has been granted approvals in several countries for use in adults and children hospitalized with severe coronavirus disease 2019 (COVID-19). Inside the cell, remdesivir undergoes metabolic activation to form the intracellular active triphosphate metabolite, GS-443902 (detected in peripheral blood mononuclear cells), and ultimately, the renally eliminated plasma metabolite GS-441524. This review discusses the pre-clinical pharmacology of RDV, clinical pharmacokinetics, pharmacodynamics/concentration-QT analysis, rationale for dose selection for treatment of patients with COVID-19, and drug-drug interaction potential based on available in vitro and clinical data in healthy volunteers. Following single-dose intravenous administration over 2 h of an RDV solution formulation across the dose range of 3-225 mg in healthy participants, RDV and its metabolites (GS-704277and GS-441524) exhibit linear pharmacokinetics. Following multiple doses of RDV 150 mg once daily for 7 or 14 days, major metabolite GS-441524 accumulates approximately 1.9-fold in plasma. Based on pharmacokinetic bridging from animal data and available human data in healthy volunteers, the RDV clinical dose regimen of a 200-mg loading dose on day 1 followed by 100-mg maintenance doses for 4 or 9 days was selected for further evaluation of pharmacokinetics and safety. Results showed high intracellular concentrations of GS-443902 suggestive of efficient conversion from RDV into the triphosphate form, and further supporting this clinical dosing regimen for the treatment of COVID-19. Mathematical drug-drug interaction liability predictions, based on in vitro and phase I data, suggest RDV has low potential for drug-drug interactions, as the impact of inducers or inhibitors on RDV disposition is minimized by the parenteral route of administration and extensive extraction. Using physiologically based pharmacokinetic modeling, RDV is not predicted to be a clinically significant inhibitor of drug-metabolizing enzymes or transporters in patients infected with COVID-19 at therapeutic RDV doses.
Topics: Adenosine; Adenosine Monophosphate; Adult; Alanine; Animals; Antiviral Agents; Area Under Curve; Dose-Response Relationship, Drug; Drug Interactions; Furans; Half-Life; Humans; Metabolic Clearance Rate; Pyrroles; SARS-CoV-2; Triazines; COVID-19 Drug Treatment
PubMed: 33782830
DOI: 10.1007/s40262-021-00984-5 -
Brain Research Bulletin Mar 2021The discovery and development of safinamide, an alpha-aminoamide, has been a valuable addition to the existing clinical management of Parkinson's disease (PD). The... (Review)
Review
The discovery and development of safinamide, an alpha-aminoamide, has been a valuable addition to the existing clinical management of Parkinson's disease (PD). The journey of safinamide dates back to the year 1983, when an alpha-aminoamide called milacemide showed a weak anticonvulsant activity. Milacemide was then structurally modified to give rise to safinamide, which in turn produced robust anticonvulsant activity. The underlying mechanism behind this action of safinamide is attributed to the inhibition of voltage gated calcium and sodium channels. Moreover, owing to the importance of ion channels in maintaining neuronal circuitry and neurotransmitter release, numerous studies explored the potential of safinamide in neurological diseases including PD, stroke, multiple sclerosis and neuromuscular disorders such as Duchenne muscular dystrophy and non-dystrophic myotonias. Nevertheless, evidence from multiple preclinical studies suggested a potent, selective and reversible inhibitory activity of safinamide against monoamine oxidase (MAO)-B enzyme which is responsible for degrading dopamine, a neurotransmitter primarily implicated in the pathophysiology of PD. Therefore, clinical studies were conducted to assess safety and efficacy of safinamide in PD. Indeed, results from various Phase 3 clinical trials suggested strong evidence of safinamide as an add-on therapy in controlling the exacerbation of PD. This review presents a thorough developmental history of safinamide in PD and provides comprehensive insight into plausible mechanisms via which safinamide can be explored in other neurological and muscular diseases.
Topics: Alanine; Animals; Anticonvulsants; Antiparkinson Agents; Benzylamines; Humans; Monoamine Oxidase; Nervous System Diseases; Parkinson Disease
PubMed: 33387637
DOI: 10.1016/j.brainresbull.2020.12.018 -
Mini Reviews in Medicinal Chemistry 2021Due to the rapidly developing nature of the current COVID-19 outbreak and its almost immediate humanitarian and economic toll, coronavirus drug discovery efforts have... (Review)
Review
Due to the rapidly developing nature of the current COVID-19 outbreak and its almost immediate humanitarian and economic toll, coronavirus drug discovery efforts have largely focused on generating potential COVID-19 drug candidates as quickly as possible. Globally, scientists are working day and night to find the best possible solution to treat the deadly virus. During the first few months of 2020, the SARS-CoV-2 outbreak quickly developed into a pandemic, with a mortality rate that was increasing at an exponential rate day by day. As a result, scientists have turned to a drug repurposing approach to rediscover the potential use and benefits of existing approved drugs. Currently, there is no single drug approved by the U.S. Food and Drug Administration (FDA), for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously known as 2019-nCoV) that causes COVID-19. Based on only in-vitro studies, several active drugs are already in the clinical pipeline, made possible by following the compassionate use of medical protocols. This method of repurposing and the use of existing molecules like Remdesivir (GS-5734), Chloroquine, Hydroxychloroquine, etc. has proven to be a landmark in the field of drug rediscovery. In this review article, we will discuss the repurposing of medicines for treating the deadly novel coronavirus (SARS-CoV-2).
Topics: Adenosine Monophosphate; Alanine; Animals; Antimalarials; Antiviral Agents; Chloroquine; Drug Discovery; Drug Repositioning; Humans; Hydroxychloroquine; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 32838716
DOI: 10.2174/1389557520999200824103803 -
Indian Journal of Pharmacology 2020
Topics: Adenosine Monophosphate; Alanine; Anti-Inflammatory Agents; Antiviral Agents; Dexamethasone; Drug Approval; Legislation, Drug; Pandemics; COVID-19 Drug Treatment
PubMed: 33666185
DOI: 10.4103/ijp.ijp_32_21 -
Journal of Environmental Sciences... Jan 2020Water-uptakes of pure sodium carbonate (NaCO), pure β-alanine and internally mixed β-alanine/NaCO aerosol particles with different mole ratios are first monitored...
Water-uptakes of pure sodium carbonate (NaCO), pure β-alanine and internally mixed β-alanine/NaCO aerosol particles with different mole ratios are first monitored using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) technique. For pure NaCO aerosol particles, combining the absorptions at 877 and 1422 cm with abrupt water loss shows the efflorescence relative humidity (ERH) of 62.9%-51.9%. Upon humidifying, solid NaCO firstly absorbs water to from NaCO·HO crystal at 72.0% RH and then deliquesces at 84.5% RH (DRH). As for pure β-alanine particles, the crystallization takes place in the range of 42.4%-33.2% RH and becomes droplets at ~88.2% RH. When β-alanine is mixed with NaCO at various mole ratios, it shows no efflorescence of NaCO when β-alanine to NaCO mole ratio (OIR) is 2:1. For 1:1 and 1:2 β-alanine/NaCO aerosols, the ERHs of NaCO are 51.8%-42.3% and 57.1%-42.3%, respectively. While β-alanine crystal appears from 62.7% RH for 2:1 and 59.4% RH for both 1:1 and 1:2 particles and lasts to driest state. On hydration, the DRH is 44.7%-75.2% for NaCO with the OIR of 1:1 and 44.7%-69.0% for 1:2 mixture, and those of β-alanine are 74.8% for 2:1 mixture and 68.9% for two others. After the first dehumidification-humidification, all the water contents decrease despite of constituent fraction. And at ~92% RH, the remaining water contents are 92%, 89% and 82% at ~92% RH, corresponding to OIR of 2:1, 1:1 and 1:2 mixed system, respectively.
Topics: Alanine; Carbonates; Models, Chemical; Spectroscopy, Fourier Transform Infrared; Wettability
PubMed: 31791498
DOI: 10.1016/j.jes.2019.07.002