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MMW Fortschritte Der Medizin Jun 2022
Review
Topics: Adenosine Monophosphate; Alanine; Hospitalization; Humans; COVID-19 Drug Treatment
PubMed: 35650486
DOI: 10.1007/s15006-022-1234-z -
Travel Medicine and Infectious Disease 2020
Topics: Adenosine Monophosphate; Alanine; Antimalarials; Antiviral Agents; Betacoronavirus; COVID-19; Coronavirus Infections; Drug Repositioning; Humans; Hydroxychloroquine; Pandemics; Pneumonia, Viral; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 32247925
DOI: 10.1016/j.tmaid.2020.101658 -
Journal of Veterinary Internal Medicine Jan 2022Rabacfosadine (RAB, Tanovea-CA1) is a novel chemotherapy agent conditionally approved for the treatment of lymphoma in dogs.
BACKGROUND
Rabacfosadine (RAB, Tanovea-CA1) is a novel chemotherapy agent conditionally approved for the treatment of lymphoma in dogs.
HYPOTHESIS/OBJECTIVES
To determine the efficacy and safety of RAB in dogs with lymphoma.
ANIMALS
One hundred and fifty-eight client-owned dogs with naïve or relapsed multicentric lymphoma were prospectively enrolled from January to October 2019.
METHODS
Dogs were randomized to receive RAB or placebo at a 3 : 1 ratio. Treatment was given every 21 days for up to 5 treatments. Study endpoints included progression-free survival (PFS), overall response rate (ORR) at a given visit, best overall response rate (BORR), and percent progression free 1 month after treatment completion. Safety data were also collected.
RESULTS
The median PFS was significantly longer in the RAB group compared to placebo (82 vs 21 days; P < .0001, HR 6.265 [95% CI 3.947-9.945]). The BORR for RAB-treated dogs was 73.2% (50.9% complete response [CR], 22.3% partial response [PR]) and 5.6% (0% CR, 5.6% PR) for placebo-treated dogs (P < .0001). One month after the last treatment, 37 RAB-treated dogs (33%) were progression free compared with no placebo-treated dogs (P < .0001). The most common adverse events observed in the RAB group were diarrhea (87.5%), decreased appetite (68.3%), and vomiting (68.3%) and were generally low grade and reversible. Serious adverse events were reported in 24 RAB-treated (20%) and 5 placebo-treated dogs (13%).
CONCLUSIONS AND CLINICAL IMPORTANCE
Rabacfosadine demonstrated statistically significant antitumor efficacy in dogs with lymphoma when administered every 21 days for up to 5 treatments as compared to placebo.
Topics: Alanine; Animals; Antineoplastic Combined Chemotherapy Protocols; Dog Diseases; Dogs; Lymphoma; Purines; Treatment Outcome
PubMed: 34952995
DOI: 10.1111/jvim.16341 -
CMAJ : Canadian Medical Association... Apr 2021
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; COVID-19; Chemical and Drug Induced Liver Injury; Critical Care; Drug Hypersensitivity; Humans; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 33824151
DOI: 10.1503/cmaj.202505-f -
European Review For Medical and... Jan 2021List the clinical data of the role of remdesivir in COVID-19, and try to make an objective evaluation and analyze its feasibility. (Review)
Review
OBJECTIVE
List the clinical data of the role of remdesivir in COVID-19, and try to make an objective evaluation and analyze its feasibility.
MATERIALS AND METHODS
The keywords of "remdesivir", "COVID-19" and "SARS-CoV-2" were systematically searched in PubMed and Web of Science. After removing the repetitions, we summarize articles, letters, and comments on remdesivir in the treatment of COVID-19.
RESULTS
In this review, we summarize clinical case of using remdesivir in the treatment of COVID-19, analyzed the final treatment results, and judged whether the drug was effective for the treatment of COVID-19. Also, attention was paid to the side effects of the drug.
CONCLUSIONS
According to the clinical results, it was found that remdesivir was effective in the treatment of COVID-19. The drug has side effects, but the symptoms were mild and disappeared immediately after discontinuation of medication.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Humans; SARS-CoV-2; Treatment Outcome; COVID-19 Drug Treatment
PubMed: 33506946
DOI: 10.26355/eurrev_202101_24426 -
d-Alanine as a biomarker and a therapeutic option for severe influenza virus infection and COVID-19.Biochimica Et Biophysica Acta.... Jan 2023Since the outbreak of coronavirus disease 2019 (COVID-19), biomarkers for evaluating severity, as well as supportive care to improve clinical course, remain...
Since the outbreak of coronavirus disease 2019 (COVID-19), biomarkers for evaluating severity, as well as supportive care to improve clinical course, remain insufficient. We explored the potential of d-amino acids, rare enantiomers of amino acids, as biomarkers for assessing disease severity and as protective nutrients against severe viral infections. In mice infected with influenza A virus (IAV) and in patients with severe COVID-19 requiring artificial ventilation or extracorporeal membrane oxygenation, blood levels of d-amino acids, including d-alanine, were reduced significantly compared with those of uninfected mice or healthy controls. In mice models of IAV infection or COVID-19, supplementation with d-alanine alleviated severity of clinical course, and mice with sustained blood levels of d-alanine showed favorable prognoses. In severe viral infections, blood levels of d-amino acids, including d-alanine, decrease, and supplementation with d-alanine improves prognosis. d-Alanine has great potentials as a biomarker and a therapeutic option for severe viral infections.
Topics: Mice; Animals; Humans; Influenza, Human; Alanine; SARS-CoV-2; Communicable Diseases; Biomarkers; COVID-19 Drug Treatment
PubMed: 36280155
DOI: 10.1016/j.bbadis.2022.166584 -
Impact of Inhibition of Glutamine and Alanine Transport on Cerebellar Glial and Neuronal Metabolism.Biomolecules Aug 2022The cerebellum, or "little brain", is often overlooked in studies of brain metabolism in favour of the cortex. Despite this, anomalies in cerebellar amino acid...
The cerebellum, or "little brain", is often overlooked in studies of brain metabolism in favour of the cortex. Despite this, anomalies in cerebellar amino acid homeostasis in a range of disorders have been reported. Amino acid homeostasis is central to metabolism, providing recycling of carbon backbones and ammonia between cell types. Here, we examined the role of cerebellar amino acid transporters in the cycling of glutamine and alanine in guinea pig cerebellar slices by inhibiting amino acid transporters and examining the resultant metabolism of [1-C]d-glucose and [1,2-C]acetate by NMR spectroscopy and LCMS. While the lack of specific inhibitors of each transporter makes interpretation difficult, by viewing results from experiments with multiple inhibitors we can draw inferences about the major cell types and transporters involved. In cerebellum, glutamine and alanine transfer is dominated by system A, blockade of which has maximum effect on metabolism, with contributions from System N. Inhibition of neural system A isoform SNAT1 by MeAIB resulted in greatly decreased metabolite pools and reduced net fluxes but showed little effect on fluxes from [1,2-C]acetate unlike inhibition of SNAT3 and other glutamine transporters by histidine where net fluxes from [1,2-C]acetate are reduced by ~50%. We interpret the data as further evidence of not one but several glutamate/glutamine exchange pools. The impact of amino acid transport inhibition demonstrates that the cerebellum has tightly coupled cells and that glutamate/glutamine, as well as alanine cycling, play a major role in that part of the brain.
Topics: Acetates; Alanine; Ammonia; Animals; Carbon; Cerebellum; Glucose; Glutamates; Glutamic Acid; Glutamine; Guinea Pigs; Histidine
PubMed: 36139028
DOI: 10.3390/biom12091189 -
The Journal of Antimicrobial... Dec 2021Mounting evidence suggests that pregnant people have an elevated risk of severe COVID-19-related complications compared with their non-pregnant counterparts,... (Review)
Review
Mounting evidence suggests that pregnant people have an elevated risk of severe COVID-19-related complications compared with their non-pregnant counterparts, underscoring the need for effective prevention and treatment strategies. However, despite progress in innovative and flexible trial designs during the COVID-19 pandemic, regressive policies excluding pregnant and breastfeeding people from biomedical research persist. Remdesivir, a broad-spectrum antiviral, was the first drug licensed for the treatment of COVID-19, based on data showing it reduced the time to recovery in hospitalized patients. Pregnant and breastfeeding people were specifically excluded from all clinical trials of remdesivir in COVID-19, but data are accumulating from post-marketing registries, compassionate use programmes and case series/reports. In this review we synthesize these data and highlight key knowledge gaps to help inform clinical decision-making about its use in pregnancy and lactation.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Breast Feeding; Female; Humans; Lactation; Pandemics; Pregnancy; Pregnancy Complications, Infectious; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34427297
DOI: 10.1093/jac/dkab311 -
Biomedicine & Pharmacotherapy =... Mar 2022Coronavirus disease 2019 (COVID-19) represents an unmet clinical need, due to a high mortality rate, rapid mutation rate in the virus, increased chances of reinfection,... (Comparative Study)
Comparative Study Review
Coronavirus disease 2019 (COVID-19) represents an unmet clinical need, due to a high mortality rate, rapid mutation rate in the virus, increased chances of reinfection, lack of effectiveness of repurposed drugs and economic damage. COVID-19 pandemic has created an urgent need for effective molecules. Clinically proven efficacy and safety profiles have made favipiravir (FVP) and remdesivir (RDV) promising therapeutic options for use against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Even though both are prodrug molecules with an antiviral role based on a similar mechanism of action, differences in pharmacological, pharmacokinetic and pharmacotoxicological mechanisms have been identified. The present study aims to provide a comprehensive comparative assessment of FVP and RDV against SARS-CoV-2 infections, by centralizing medical data provided by significant literature and authorized clinical trials, focusing on the importance of a better understanding of the interactions between drug molecules and infectious agents in order to improve the global management of COVID-19 patients and to reduce the risk of antiviral resistance.
Topics: Adenosine Monophosphate; Alanine; Amides; Antiviral Agents; Humans; Pyrazines; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35131656
DOI: 10.1016/j.biopha.2022.112700 -
ELife Nov 2021Bacteria commonly live in spatially structured biofilm assemblages, which are encased by an extracellular matrix. Metabolic activity of the cells inside biofilms causes...
Bacteria commonly live in spatially structured biofilm assemblages, which are encased by an extracellular matrix. Metabolic activity of the cells inside biofilms causes gradients in local environmental conditions, which leads to the emergence of physiologically differentiated subpopulations. Information about the properties and spatial arrangement of such metabolic subpopulations, as well as their interaction strength and interaction length scales are lacking, even for model systems like colony biofilms grown on agar-solidified media. Here, we use an unbiased approach, based on temporal and spatial transcriptome and metabolome data acquired during colony biofilm growth, to study the spatial organization of metabolism. We discovered that alanine displays a unique pattern among amino acids and that alanine metabolism is spatially and temporally heterogeneous. At the anoxic base of the colony, where carbon and nitrogen sources are abundant, cells secrete alanine the transporter AlaE. In contrast, cells utilize alanine as a carbon and nitrogen source in the oxic nutrient-deprived region at the colony mid-height, the enzymes DadA and DadX. This spatially structured alanine cross-feeding influences cellular viability and growth in the cross-feeding-dependent region, which shapes the overall colony morphology. More generally, our results on this precisely controllable biofilm model system demonstrate a remarkable spatiotemporal complexity of metabolism in biofilms. A better characterization of the spatiotemporal metabolic heterogeneities and dependencies is essential for understanding the physiology, architecture, and function of biofilms.
Topics: Alanine; Biofilms; Escherichia coli; Metabolome; Spatial Analysis; Transcriptome
PubMed: 34751128
DOI: 10.7554/eLife.70794