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Drug Design, Development and Therapy 2016Safinamide (SAF) is a new drug developed for the treatment of Parkinson's disease (PD). It is a benzylamino derivative with multiple mechanisms of action and... (Review)
Review
Safinamide (SAF) is a new drug developed for the treatment of Parkinson's disease (PD). It is a benzylamino derivative with multiple mechanisms of action and antiparkinsonian, anticonvulsant, and neuroprotective properties. SAF inhibits monoamine oxidase B and dopamine reuptake and glutamate release, blocks voltage-dependent sodium channels, and modulates calcium channels. Although the antiparkinsonian effect can be ascribed in part to the inhibition of the monoamine oxidase B, which is complete at 50 mg, the enhanced benefit seen at the 100 mg dose is probably due to nondopaminergic mechanisms. SAF will represent an important option for patients with both early and advanced PD. In early PD patients, the addition of SAF to dopamine agonists may be an effective treatment strategy to improve motor function, prolong the use of dopamine agonists, and/or delay the introduction of levodopa. In advanced parkinsonian patients, SAF has been demonstrated to significantly increase on time with no, or nontroublesome dyskinesias. All studies performed have demonstrated its efficacy in benefiting both short-term and long-term quality-of-life outcomes in both early and advanced PD patients. SAF has been investigated in long-term (24 months), double-blind, placebo-controlled studies, where it showed a very good safety profile. SAF has not been studied in de novo PD patients, and its potential positive effect on dyskinesia deserves further dedicated studies.
Topics: Adult; Aged; Alanine; Benzylamines; Double-Blind Method; Humans; Middle Aged; Monoamine Oxidase Inhibitors; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 26917951
DOI: 10.2147/DDDT.S77749 -
Molecules (Basel, Switzerland) Feb 2023A comparative investigation of amino acids (proline, cysteine, and alanine) as dosimetric materials using electron paramagnetic resonance (EPR) spectroscopy in the...
A comparative investigation of amino acids (proline, cysteine, and alanine) as dosimetric materials using electron paramagnetic resonance (EPR) spectroscopy in the absorbed dosage range of 1-25 kGy is presented. There were no signals in the EPR spectra of the samples before irradiation. After irradiation, the complex spectra were recorded. These results showed that the investigated amino acids were sensitive to radiation. In the EPR spectrum of cysteine after irradiation, RS• radicals dominated. The effects of the microwave power on the saturation of the EPR signals showed the presence of at least three different types of free radicals in proline. It was also found out that the DL-proline and cysteine had stable free radicals after irradiation and represented a linear dosage response up to 10 kGy. On the other hand, the amino acid alanine has been accepted by the International Atomic Energy Agency as a transfer standard dosimetry system. In view of this, the obtained results of the proline and cysteine studies have been compared with those of the alanine studies. The results showed that the amino acids proline and cysteine could be used as alternative dosimetric materials in lieu of alanine in a dosage range of 1-10 kGy of an absorbed dose of γ-rays using EPR spectroscopy. Regarding the radiation sensitivity, the following order of decreased dosage responses was determined: alanine > DL-proline > cysteine > L-proline.
Topics: Amino Acids; Electron Spin Resonance Spectroscopy; Cysteine; Alanine; Proline; Free Radicals
PubMed: 36838733
DOI: 10.3390/molecules28041745 -
Lancet (London, England) May 2022
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Humans
PubMed: 35512729
DOI: 10.1016/S0140-6736(22)00789-9 -
Journal of Infection and Chemotherapy :... Jan 2023Healthcare-associated COVID-19 among vulnerable patients leads to disproportionate morbidity and mortality. Early pharmacologic intervention may reduce negative sequelae... (Review)
Review
Healthcare-associated COVID-19 among vulnerable patients leads to disproportionate morbidity and mortality. Early pharmacologic intervention may reduce negative sequelae and improve survival in such settings. This study aimed to describe outcome of patients with healthcare-associated COVID-19 who received early short-course remdesivir therapy. We reviewed the characteristics and outcome of hospitalized patients who developed COVID-19 during an outbreak that involved two wards at a non-acute care hospital in Japan and received short-course remdesivir. Forty-nine patients were diagnosed with COVID-19, 34 on a comprehensive inpatient rehabilitation ward and 15 on a combined palliative care and internal medicine ward. Forty-seven were symptomatic and 46 of them received remdesivir. The median age was 75, and the median Charlson comorbidity index was 6 among those who received it. Forty-one patients had received one or two doses of mRNA vaccines, while none had received a third dose. Most patients received 3 days of remdesivir. Of the patients followed up to 14 and 28 days from onset, 41/44 (95.3%) and 35/41(85.4%) were alive, respectively. Six deaths occurred by 28 days in the palliative care/internal medicine ward and two of them were possibly related to COVID-19. Among those who survived, the performance status was unchanged between the time of onset and at 28 days.
Topics: Humans; Aged; SARS-CoV-2; Antiviral Agents; Alanine; Delivery of Health Care; Hospitals; COVID-19 Drug Treatment
PubMed: 36113848
DOI: 10.1016/j.jiac.2022.08.025 -
Neurologia Sep 2020
Topics: Alanine; Antiparkinson Agents; Benzylamines; Sexuality
PubMed: 30551909
DOI: 10.1016/j.nrl.2018.07.004 -
Expert Review of Proteomics Jul 2018Measuring the immediate changes in cells that arise from changing environmental conditions is crucial to understanding the underlying mechanisms involved. These changes... (Review)
Review
Measuring the immediate changes in cells that arise from changing environmental conditions is crucial to understanding the underlying mechanisms involved. These changes can be measured with metabolic stable isotope fully labeled proteomes, but requires looking for changes in the midst of a large background. In addition, labeling efficiency can be an issue in primary and fully differentiated cells. Area covered: Azidohomoalanine (AHA), an analog of methionine, can be accepted by cellular translational machinery and incorporated into newly synthesized proteins (NSPs). AHA-NSPs can be coupled to biotin via CuAAC-mediated click-chemistry and enriched using avidin-based affinity purification. Thus, AHA-containing proteins or peptides can be enriched and efficiently separated from the whole proteome. In this review, we describe the development of mass spectrometry (MS) based AHA strategies and discuss their potential to measure proteins involved in immune response, secretome, gut microbiome, and proteostasis as well as their potential for clinical uses. Expert commentary: AHA strategies have been used to identify synthesis activity and to compare two biological conditions in various biological model organisms. In combination with instrument development, improved sample preparation and fractionation strategies, MS-based AHA strategies have the potential for broad application, and the methods should translate into clinical use.
Topics: Alanine; Animals; Humans; Immunity; Isotope Labeling; Microbiota; Protein Biosynthesis; Proteomics; Proteostasis
PubMed: 30005169
DOI: 10.1080/14789450.2018.1500902 -
Bioinformatics (Oxford, England) Oct 2022Poly-alanine (polyA) regions are protein stretches mostly composed of alanines. Despite their abundance in eukaryotic proteomes and their association to nine inherited...
MOTIVATION
Poly-alanine (polyA) regions are protein stretches mostly composed of alanines. Despite their abundance in eukaryotic proteomes and their association to nine inherited human diseases, the structural and functional roles exerted by polyA stretches remain poorly understood. In this work we study how the amino acid context in which polyA regions are settled in proteins influences their structure and function.
RESULTS
We identified glycine and proline as the most abundant amino acids within polyA and in the flanking regions of polyA tracts, in human proteins as well as in 17 additional eukaryotic species. Our analyses indicate that the non-structuring nature of these two amino acids influences the α-helical conformations predicted for polyA, suggesting a relevant role in reducing the inherent aggregation propensity of long polyA. Then, we show how polyA position in protein N-termini relates with their function as transit peptides. PolyA placed just after the initial methionine is often predicted as part of mitochondrial transit peptides, whereas when placed in downstream positions, polyA are part of signal peptides. A few examples from known structures suggest that short polyA can emerge by alanine substitutions in α-helices; but evolution by insertion is observed for longer polyA. Our results showcase the importance of studying the sequence context of homorepeats as a mechanism to shape their structure-function relationships.
AVAILABILITY AND IMPLEMENTATION
The datasets used and/or analyzed during the current study are available from the corresponding author onreasonable request.
SUPPLEMENTARY INFORMATION
Supplementary data are available at Bioinformatics online.
Topics: Humans; Alanine; Poly A; Amino Acid Sequence; Proteome; Peptides
PubMed: 36106994
DOI: 10.1093/bioinformatics/btac610 -
Journal of Biomaterials Applications Apr 2016In order to overcome major problems regarding the lack of affinity to solvents and limited reactivity of the free amines of chitosan, introduction of appropriate spacer...
In order to overcome major problems regarding the lack of affinity to solvents and limited reactivity of the free amines of chitosan, introduction of appropriate spacer arms having terminal amine function is considered of interest. L-Alanine-N-carboxyanhydride was grafted onto chitosan via anionic ring-opening polymerization. The chemical and structural characterizations of L-alanine-grafted chitosan (Ala-g-Cts) were confirmed through Fourier transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy ((1)H NMR). In addition, the viscoelastic properties of Ala-g-Cts were examined by means of a rotational viscometer, and thermal analysis was carried out with a thermogravimetric analyzer and differential scanning calorimetry. Morphological changes in the chitosan L-alanine moiety were determined by x-ray diffraction. To determine the feasibility of using these films as biomedical materials, we investigated the effects of their L-alanine content on physical and mechanical properties. The biodegradation results of crosslinked Ala-g-Cts films were evaluated in phosphate-buffered solution containing lysozyme at 37℃. Proliferation of MC3T3-E1 cells on crosslinked Ala-g-Cts films was also investigated with use of the CCK-8 assay.
Topics: Alanine; Animals; Biocompatible Materials; Cell Line; Cell Proliferation; Chickens; Chitosan; Magnetic Resonance Spectroscopy; Materials Testing; Mice; Muramidase; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction
PubMed: 26767393
DOI: 10.1177/0885328215626892 -
International Journal of Molecular... Nov 2019A central question in the evolution of the modern translation machinery is the origin and chemical ethology of the amino acids prescribed by the genetic code. The RNA... (Review)
Review
A central question in the evolution of the modern translation machinery is the origin and chemical ethology of the amino acids prescribed by the genetic code. The RNA World hypothesis postulates that templated protein synthesis has emerged in the transition from RNA to the Protein World. The sequence of these events and principles behind the acquisition of amino acids to this process remain elusive. Here we describe a model for this process by following the scheme previously proposed by Hartman and Smith, which suggests gradual expansion of the coding space as GC-GCA-GCAU genetic code. We point out a correlation of this scheme with the hierarchy of the protein folding. The model follows the sequence of steps in the process of the amino acid recruitment and fits well with the co-evolution and coenzyme handle theories. While the starting set (GC-phase) was responsible for the nucleotide biosynthesis processes, in the second phase alanine-based amino acids (GCA-phase) were recruited from the core metabolism, thereby providing a standard secondary structure, the α-helix. In the final phase (GCAU-phase), the amino acids were appended to the already existing architecture, enabling tertiary fold and membrane interactions. The whole scheme indicates strongly that the choice for the alanine core was done at the GCA-phase, while glycine and proline remained rudiments from the GC-phase. We suggest that the Protein World should rather be considered the Alanine World, as it predominantly relies on the alanine as the core chemical scaffold.
Topics: Alanine; Amino Acids; Animals; Evolution, Molecular; Genetic Code; Humans; Protein Biosynthesis; Protein Folding; Proteins
PubMed: 31694194
DOI: 10.3390/ijms20215507 -
Journal of Comparative Effectiveness... Dec 2020The race to find an effective treatment for coronavirus disease 2019 (COVID-19) is still on, with only two treatment options currently authorized for emergency use... (Review)
Review
The race to find an effective treatment for coronavirus disease 2019 (COVID-19) is still on, with only two treatment options currently authorized for emergency use and/or recommended for patients hospitalized with severe respiratory symptoms: low-dose dexamethasone and remdesivir. The USA decision to stockpile the latter has resulted in widespread condemnation and in similar action being taken by some other countries. In this commentary we discuss whether stockpiling remdesivir is justified in light of the currently available evidence.
Topics: Adenosine Monophosphate; Alanine; Antiviral Agents; Humans; International Cooperation; Internationality; SARS-CoV-2; Strategic Stockpile; United States; COVID-19 Drug Treatment
PubMed: 33274643
DOI: 10.2217/cer-2020-0174