Displaying publications 21 - 40 of 137 in total

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  1. Fulltext Rapid review of suspected adverse drug events due to remdesivir in the WHO database; findings and implications
    Charan J, Kaur RJ, Bhardwaj P, Haque M, Sharma P, Misra S, et al.
    Expert Rev Clin Pharmacol, 2021 Jan;14(1):95-103.
    PMID: 33252992 DOI: 10.1080/17512433.2021.1856655
    Objectives: Remdesivir has shown promise in the management of patients with COVID-19 although recent studies have shown concerns with its effectiveness in practice. Despite this there is a need to document potential adverse drug events (ADEs) to guide future decisions as limited ADE data available before the COVID-19 pandemic. Methods: Interrogation of WHO VigiBase® from 2015 to 2020 coupled with published studies of ADEs in COVID-19 patients. The main outcome measures are the extent of ADEs broken down by factors including age, seriousness, region and organ. Results: A total 1086 ADEs were reported from the 439 individual case reports up to July 19, 2020, in the VigiBase®, reduced to 1004 once duplicates were excluded. Almost all ADEs concerned COVID-19 patients (92.5%), with an appreciable number from the Americas (67.7%). The majority of ADEs were from males > 45 years and were serious (82.5%). An increase in hepatic enzymes (32.1%), renal injury (14.4%), rise in creatinine levels (11.2%), and respiratory failure (6.4%) were the most frequently reported ADEs. Conclusions: Deterioration of liver and kidney function are frequently observed ADEs with remdesivir; consequently, patients should be monitored for these ADEs. The findings are in line with ADEs included in regulatory authority documents.
    Matched MeSH terms: Adenosine Monophosphate/adverse effects; Adenosine Monophosphate/analogs & derivatives*; Adenosine Monophosphate/therapeutic use
  2. Molecular dynamics simulations of the adenosine A2a receptor in POPC and POPE lipid bilayers: effects of membrane on protein behavior
    Ng HW, Laughton CA, Doughty SW
    J Chem Inf Model, 2014 Feb 24;54(2):573-81.
    PMID: 24460123 DOI: 10.1021/ci400463z
    Analysis of 300 ns (ns) molecular dynamics (MD) simulations of an adenosine A2a receptor (A2a AR) model, conducted in triplicate, in 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) and 1-palmitoyl-2-oleoylphosphatidylethanolamine (POPE) bilayers reveals significantly different protein dynamical behavior. Principal component analysis (PCA) shows that the dissimilarities stem from interhelical rather than intrahelical motions. The difference in the hydrophobic thicknesses of these simulated lipid bilayers is potentially a significant reason for the observed difference in results. The distinct lipid headgroups might also lead to different molecular interactions and hence different protein loop motions. Overall, the A2a AR shows higher mobility and flexibility in POPC as compared to POPE.
    Matched MeSH terms: Receptor, Adenosine A2A/metabolism*; Receptor, Adenosine A2A/chemistry
  3. Molecular dynamics simulations of the adenosine A2a receptor: structural stability, sampling, and convergence
    Ng HW, Laughton CA, Doughty SW
    J Chem Inf Model, 2013 May 24;53(5):1168-78.
    PMID: 23514445 DOI: 10.1021/ci300610w
    Molecular dynamics (MD) simulations of membrane-embedded G-protein coupled receptors (GPCRs) have rapidly gained popularity among the molecular simulation community in recent years, a trend which has an obvious link to the tremendous pharmaceutical importance of this group of receptors and the increasing availability of crystal structures. In view of the widespread use of this technique, it is of fundamental importance to ensure the reliability and robustness of the methodologies so they yield valid results and enable sufficiently accurate predictions to be made. In this work, 200 ns simulations of the A2a adenosine receptor (A2a AR) have been produced and evaluated in the light of these requirements. The conformational dynamics of the target protein, as obtained from replicate simulations in both the presence and absence of an inverse agonist ligand (ZM241385), have been investigated and compared using principal component analysis (PCA). Results show that, on this time scale, convergence of the replicates is not readily evident and dependent on the types of the protein motions considered. Thus rates of inter- as opposed to intrahelical relaxation and sampling can be different. When studied individually, we find that helices III and IV have noticeably greater stability than helices I, II, V, VI, and VII in the apo form. The addition of the inverse agonist ligand greatly improves the stability of all helices.
    Matched MeSH terms: Receptor, Adenosine A2A/metabolism*; Receptor, Adenosine A2A/chemistry*
  4. Fulltext The use of remdesivir for the management of patients with moderate-to-severe COVID-19: a systematic review
    Thiruchelvam K, Kow CS, Hadi MA, Hasan SS
    Expert Rev Anti Infect Ther, 2022 02;20(2):211-229.
    PMID: 34192469 DOI: 10.1080/14787210.2021.1949984
    OBJECTIVE: We systematically reviewed the evidence of published original research to determine the role of remdesivir in the management of patients with COVID-19 and a moderate-to-severe course of illness.

    METHODS: A systematic search of articles was conducted in scientific databases, with the latest update in May 2021. This paper systematically reviewed the clinical evidence available (randomized controlled trials, compassionate use studies, and case reports) on the use of remdesivir for patients with moderate or severe COVID-19.

    RESULTS: A total of eleven studies were included: four studies based on compassionate use of remdesivir, three randomized, double-blind, placebo-controlled, multicentre trials, three randomized, open-label, phase III trials, and one case report. Clinical improvement and mortality rates in patients who used remdesivir varied across studies.

    CONCLUSION: Given the current evidence, there is insufficient data to confidently recommend the use of remdesivir alone for the treatment of adult hospitalized patients with moderate-to-severe COVID-19. However, remdesivir may be considered along with an anti-inflammatory agent in patients with pneumonia, on oxygen support, provided there is close monitoring of clinical and laboratory parameters and adverse events.

    Matched MeSH terms: Adenosine Monophosphate/analogs & derivatives*; Adenosine Monophosphate/therapeutic use
  5. In vitro capacity of different grades of chitosan derivatives to induce platelet adhesion and aggregation
    Periayah MH, Halim AS, Hussein AR, Saad AZ, Rashid AH, Noorsal K
    Int J Biol Macromol, 2013 Jan;52:244-9.
    PMID: 23063426 DOI: 10.1016/j.ijbiomac.2012.10.001
    Chitosan-derived hemostatic agents with various formulations may have distinct potential in hemostasis. This study assessed the ability of different grades and forms of chitosan derivatives as hemostatic agents to enhance platelet adhesion and aggregation in vitro. The chitosan derivatives utilized were 2% NO-CMC, 7% NO-CMC (with 0.45 mL collagen), 8% NO-CMC, O-C 52, 5% O-CMC-47, NO-CMC-35, and O-C 53. Samples of chitosan derivatives weighing 5mg were incubated at 37°C with 50 μL of phosphate buffer saline (PBS) (pH 7.4) for 60 min. The morphological features of the platelets upon adherence to the chitosan were viewed using scanning electron microscope (SEM), and the platelet count was analyzed with an Automated Hematology Analyzer. For platelet aggregation, we added an adenosine diphosphate (ADP) agonist to induce the chitosan-adhered platelets. O-C 52 bound with platelets exhibited platelet aggregates and clumps on the surface of the membrane layer with approximately 70-80% coverage. A statistically significant correlation (p<0.01) for the platelet count was identified between the baseline value and the values at 10 min and 20 min. The results indicate that O-C 53 and O-C 52 were able to promote clotting have the potential to induce the release of platelets engaged in the process of hemostasis.
    Matched MeSH terms: Adenosine Diphosphate/metabolism; Adenosine Diphosphate/agonists
  6. Fulltext Draft genome of Brugia pahangi: high similarity between B. pahangi and B. malayi
    Lau YL, Lee WC, Xia J, Zhang G, Razali R, Anwar A, et al.
    Parasit Vectors, 2015;8:451.
    PMID: 26350613 DOI: 10.1186/s13071-015-1064-2
    Efforts to completely eradicate lymphatic filariasis from human population may be challenged by the emergence of Brugia pahangi as another zoonotic lymphatic filarial nematode. In this report, a genomic study was conducted to understand this species at molecular level.
    Matched MeSH terms: Adenosine Triphosphatases/genetics; Adenosine Triphosphatases/metabolism
  7. Have we found the panacea to COVID-19 with remdesivir, an old but newly packaged drug?
    Thalha AMM, Lee YY, Besari A, Omar SFS
    J R Coll Physicians Edinb, 2020 06;50(2):159-161.
    PMID: 32568289 DOI: 10.4997/JRCPE.2020.217
    Matched MeSH terms: Adenosine Monophosphate/analogs & derivatives*; Adenosine Monophosphate/therapeutic use
  8. Fulltext Quality of adverse event reporting in clinical trials of remdesivir in patients with COVID-19
    Kow CS, Aldeyab M, Hasan SS
    Eur J Clin Pharmacol, 2021 Mar;77(3):435-437.
    PMID: 33011825 DOI: 10.1007/s00228-020-03008-6
    Matched MeSH terms: Adenosine Monophosphate/adverse effects; Adenosine Monophosphate/analogs & derivatives*
  9. Fulltext Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses
    WHO Solidarity Trial Consortium
    Lancet, 2022 May 21;399(10339):1941-1953.
    PMID: 35512728 DOI: 10.1016/S0140-6736(22)00519-0
    BACKGROUND: The Solidarity trial among COVID-19 inpatients has previously reported interim mortality analyses for four repurposed antiviral drugs. Lopinavir, hydroxychloroquine, and interferon (IFN)-β1a were discontinued for futility but randomisation to remdesivir continued. Here, we report the final results of Solidarity and meta-analyses of mortality in all relevant trials to date.

    METHODS: Solidarity enrolled consenting adults (aged ≥18 years) recently hospitalised with, in the view of their doctor, definite COVID-19 and no contraindication to any of the study drugs, regardless of any other patient characteristics. Participants were randomly allocated, in equal proportions between the locally available options, to receive whichever of the four study drugs (lopinavir, hydroxychloroquine, IFN-β1a, or remdesivir) were locally available at that time or no study drug (controls). All patients also received the local standard of care. No placebos were given. The protocol-specified primary endpoint was in-hospital mortality, subdivided by disease severity. Secondary endpoints were progression to ventilation if not already ventilated, and time-to-discharge from hospital. Final log-rank and Kaplan-Meier analyses are presented for remdesivir, and are appended for all four study drugs. Meta-analyses give weighted averages of the mortality findings in this and all other randomised trials of these drugs among hospital inpatients. Solidarity is registered with ISRCTN, ISRCTN83971151, and ClinicalTrials.gov, NCT04315948.

    FINDINGS: Between March 22, 2020, and Jan 29, 2021, 14 304 potentially eligible patients were recruited from 454 hospitals in 35 countries in all six WHO regions. After the exclusion of 83 (0·6%) patients with a refuted COVID-19 diagnosis or encrypted consent not entered into the database, Solidarity enrolled 14 221 patients, including 8275 randomly allocated (1:1) either to remdesivir (ten daily infusions, unless discharged earlier) or to its control (allocated no study drug although remdesivir was locally available). Compliance was high in both groups. Overall, 602 (14·5%) of 4146 patients assigned to remdesivir died versus 643 (15·6%) of 4129 assigned to control (mortality rate ratio [RR] 0·91 [95% CI 0·82-1·02], p=0·12). Of those already ventilated, 151 (42·1%) of 359 assigned to remdesivir died versus 134 (38·6%) of 347 assigned to control (RR 1·13 [0·89-1·42], p=0·32). Of those not ventilated but on oxygen, 14·6% assigned to remdesivir died versus 16·3% assigned to control (RR 0·87 [0·76-0·99], p=0·03). Of 1730 not on oxygen initially, 2·9% assigned to remdesivir died versus 3·8% assigned to control (RR 0·76 [0·46-1·28], p=0·30). Combining all those not ventilated initially, 11·9% assigned to remdesivir died versus 13·5% assigned to control (RR 0·86 [0·76-0·98], p=0·02) and 14·1% versus 15·7% progressed to ventilation (RR 0·88 [0·77-1·00], p=0·04). The non-prespecified composite outcome of death or progression to ventilation occurred in 19·6% assigned to remdesivir versus 22·5% assigned to control (RR 0·84 [0·75-0·93], p=0·001). Allocation to daily remdesivir infusions (vs open-label control) delayed discharge by about 1 day during the 10-day treatment period. A meta-analysis of mortality in all randomised trials of remdesivir versus no remdesivir yielded similar findings.

    INTERPRETATION: Remdesivir has no significant effect on patients with COVID-19 who are already being ventilated. Among other hospitalised patients, it has a small effect against death or progression to ventilation (or both).

    FUNDING: WHO.

    Matched MeSH terms: Adenosine Monophosphate/analogs & derivatives; Adenosine Monophosphate/therapeutic use
  10. Fulltext Elevated-Temperature Performance, Combustibility and Fire Propagation Index of Fly Ash-Metakaolin Blend Geopolymers with Addition of Monoaluminium Phosphate (MAP) and Aluminum Dihydrogen Triphosphate (ATP)
    Zulkifly K, Cheng-Yong H, Yun-Ming L, Bayuaji R, Abdullah MMAB, Ahmad SB, et al.
    Materials (Basel), 2021 Apr 15;14(8).
    PMID: 33920865 DOI: 10.3390/ma14081973
    Thermal performance, combustibility, and fire propagation of fly ash-metakaolin (FA-MK) blended geopolymer with the addition of aluminum triphosphate, ATP (Al(H2PO4)3), and monoaluminium phosphate, MAP (AlPO4) were evaluated in this paper. To prepare the geopolymer mix, fly ash and metakaolin with a ratio of 1:1 were added with ATP and MAP in a range of 0-3% by weight. The fire/heat resistance was evaluated by comparing the residual compressive strengths after the elevated temperature exposure. Besides, combustibility and fire propagation tests were conducted to examine the thermal performance and the applicability of the geopolymers as passive fire protection. Experimental results revealed that the blended geopolymers with 1 wt.% of ATP and MAP exhibited higher compressive strength and denser geopolymer matrix than control geopolymers. The effect of ATP and MAP addition was more obvious in unheated geopolymer and little improvement was observed for geopolymer subjected to elevated temperature. ATP and MAP at 3 wt.% did not help in enhancing the elevated-temperature performance of blended geopolymers. Even so, all blended geopolymers, regardless of the addition of ATP and MAP, were regarded as the noncombustible materials with negligible (0-0.1) fire propagation index.
    Matched MeSH terms: Adenosine Triphosphate
  11. Fulltext Metabolome analysis and chemical profiling of Indonesian royal jellies as the raw material for cosmetic and bio-supplement products
    Sari E, Mahira KF, Patel DN, Chua LS, Pratami DK, Sahlan M
    Heliyon, 2021 May;7(5):e06912.
    PMID: 34013079 DOI: 10.1016/j.heliyon.2021.e06912
    Royal jellies (RJs) possess moisturizing, emulsifying, and stabilizing properties, and several pharmacological activities have also been found to be present, which make them an ideal component for cosmetic and skin care products. However, despite the abundant efficacies, there is a lack of studies that explore the chemical composition of RJ using metabolome analysis. Furthermore, an evaluation of the chemical composition of Indonesian RJs collected from different regions has yet to be carried out. Therefore, the main objective of this study was to identify any differences in the chemical composition of such RJs. Chemical profiling was also carried out to enable more targeted utilization based on the actual compositions. Chemical profiling is also important given the rich Indonesian biodiversity and the high dependence of the RJ compositions on the botanical source. In this research, ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used as part of an untargeted metabolomics approach. From the chemical profiling, >30 compounds were identified across four RJ samples. The major constituents of the samples were found to be oligosaccharides, fatty acids, and adenosine monophosphate derivatives. Meanwhile, sucrose and planteose were found to be highest in the samples from Banjarnegara and Kediri, whereas dimethyloctanoic acid was found to be unique to the sample from Banjarnegara. It was also discovered that the RJs from Demak and Tuban contained more organic fatty acids and oligosaccharides than the other samples. Although the sample from Demak demonstrated good potential for use in the cosmetic, skin care, and bio-supplement industries, the higher abundance of fatty acids and oligosaccharides in the sample from Tuban indicated that it is perhaps the most suitable RJ for use in this field.
    Matched MeSH terms: Adenosine Monophosphate
  12. Fulltext Directionally-Enhanced Binary Multi-Objective Particle Swarm Optimisation for Load Balancing in Software Defined Networks
    Albowarab MH, Zakaria NA, Zainal Abidin Z
    Sensors (Basel), 2021 May 12;21(10).
    PMID: 34065920 DOI: 10.3390/s21103356
    Various aspects of task execution load balancing of Internet of Things (IoTs) networks can be optimised using intelligent algorithms provided by software-defined networking (SDN). These load balancing aspects include makespan, energy consumption, and execution cost. While past studies have evaluated load balancing from one or two aspects, none has explored the possibility of simultaneously optimising all aspects, namely, reliability, energy, cost, and execution time. For the purposes of load balancing, implementing multi-objective optimisation (MOO) based on meta-heuristic searching algorithms requires assurances that the solution space will be thoroughly explored. Optimising load balancing provides not only decision makers with optimised solutions but a rich set of candidate solutions to choose from. Therefore, the purposes of this study were (1) to propose a joint mathematical formulation to solve load balancing challenges in cloud computing and (2) to propose two multi-objective particle swarm optimisation (MP) models; distance angle multi-objective particle swarm optimization (DAMP) and angle multi-objective particle swarm optimization (AMP). Unlike existing models that only use crowding distance as a criterion for solution selection, our MP models probabilistically combine both crowding distance and crowding angle. More specifically, we only selected solutions that had more than a 0.5 probability of higher crowding distance and higher angular distribution. In addition, binary variants of the approaches were generated based on transfer function, and they were denoted by binary DAMP (BDAMP) and binary AMP (BAMP). After using MOO mathematical functions to compare our models, BDAMP and BAMP, with state of the standard models, BMP, BDMP and BPSO, they were tested using the proposed load balancing model. Both tests proved that our DAMP and AMP models were far superior to the state of the art standard models, MP, crowding distance multi-objective particle swarm optimisation (DMP), and PSO. Therefore, this study enables the incorporation of meta-heuristic in the management layer of cloud networks.
    Matched MeSH terms: Adenosine Monophosphate
  13. Analysis of core protein clusters identifies candidate variable sites conferring metronidazole resistance in Helicobacter pylori
    Chua EG, Debowski AW, Webberley KM, Peters F, Lamichhane B, Loke MF, et al.
    Gastroenterol Rep (Oxf), 2019 Feb;7(1):42-49.
    PMID: 30792865 DOI: 10.1093/gastro/goy048
    Background: Metronidazole is one of the first-line drugs of choice in the standard triple therapy used to eradicate Helicobacter pylori infection. Hence, the global emergence of metronidazole resistance in Hp poses a major challenge to health professionals. Inactivation of RdxA is known to be a major mechanism of conferring metronidazole resistance in H. pylori. However, metronidazole resistance can also arise in H. pylori strains expressing functional RdxA protein, suggesting that there are other mechanisms that may confer resistance to this drug.

    Methods: We performed whole-genome sequencing on 121 H. pylori clinical strains, among which 73 were metronidazole-resistant. Sequence-alignment analysis of core protein clusters derived from clinical strains containing full-length RdxA was performed. Variable sites in each alignment were statistically compared between the resistant and susceptible groups to determine candidate genes along with their respective amino-acid changes that may account for the development of metronidazole resistance in H. pylori.

    Results: Resistance due to RdxA truncation was identified in 34% of metronidazole-resistant strains. Analysis of core protein clusters derived from the remaining 48 metronidazole-resistant strains and 48 metronidazole-susceptible identified four variable sites significantly associated with metronidazole resistance. These sites included R16H/C in RdxA, D85N in the inner-membrane protein RclC (HP0565), V265I in a biotin carboxylase protein (HP0370) and A51V/T in a putative threonylcarbamoyl-AMP synthase (HP0918).

    Conclusions: Our approach identified new potential mechanisms for metronidazole resistance in H. pylori that merit further investigation.

    Matched MeSH terms: Adenosine Monophosphate
  14. Germline mutation and protein expression analysis of mismatch repair genes MSH6 and PMS2 in Malaysian Lynch syndrome patients
    Zahary MN, Kaur G, Hassan MR, Sidek AS, Singh H, Yeh LY, et al.
    Int J Colorectal Dis, 2014 Feb;29(2):261-2.
    PMID: 24072394 DOI: 10.1007/s00384-013-1770-1
    Matched MeSH terms: Adenosine Triphosphatases/genetics*
  15. Mitochondrial respiratory function and antioxidant capacity in normal and cirrhotic livers following partial hepatectomy
    Yang S, Tan TM, Wee A, Leow CK
    Cell Mol Life Sci, 2004 Jan;61(2):220-9.
    PMID: 14745500
    For many liver malignancies, major hepatectomy is the usual therapy. Although a normal liver has a tremendous capacity for regeneration, liver hepatectomy in humans is usually carried out on a diseased liver and, in such cases, liver regeneration takes place in a cirrhotic remnant. Mitochondrial function in cirrhotic livers shows a variety of changes compared to control livers. This study investigated how mitochondrial respiratory function and antioxidant capacity change following partial hepatectomy of cirrhotic livers, because liver regeneration requires greater energy demands and control of oxidative stress. Cirrhosis was induced in male Wistar-Furth rats by administration of thioacetamide. NADH-cytochrome c reductase activity, mitochondrial glutathione peroxidase activity and mitochondrial GSH levels were all significantly lowered in cirrhotic livers and in the cirrhotic remnants up to 72 h after 70% hepatectomy when compared to the corresponding controls. Lower respiratory control ratios with succinate as substrate were also observed from 6 to 48 h post-hepatectomy. At 24 h post-hepatectomy, higher levels of lipid peroxidation were observed. We conclude that, compared to the controls, cirrhotic livers have diminished oxidative phosphorylation capabilities due to changes in NADH and FADH(2)-linked respiration as well as impaired antioxidant defenses following partial hepatectomy. Both of these factors, if critical, could then impede liver regeneration.
    Matched MeSH terms: Adenosine Triphosphatases/metabolism
  16. Adenosine Receptors as Novel Targets for the Treatment of Various Cancers
    Gorain B, Choudhury H, Yee GS, Bhattamisra SK
    Curr Pharm Des, 2019;25(26):2828-2841.
    PMID: 31333092 DOI: 10.2174/1381612825666190716102037
    Adenosine is a ubiquitous signaling nucleoside molecule, released from different cells within the body to act on vasculature and immunoescape. The physiological action on the proliferation of tumour cell has been reported by the presence of high concentration of adenosine within the tumour microenvironment, which results in the progression of the tumour, even leading to metastases. The activity of adenosine exclusively depends upon the interaction with four subtypes of heterodimeric G-protein-coupled adenosine receptors (AR), A1, A2A, A2B, and A3-ARs on the cell surface. Research evidence supports that the activation of those receptors via specific agonist or antagonist can modulate the proliferation of tumour cells. The first category of AR, A1 is known to play an antitumour activity via tumour-associated microglial cells to prevent the development of glioblastomas. A2AAR are found in melanoma, lung, and breast cancer cells, where tumour proliferation is stimulated due to inhibition of the immune response via inhibition of natural killer cells cytotoxicity, T cell activity, and tumourspecific CD4+/CD8+ activity. Alternatively, A2BAR helps in the development of tumour upon activation via upregulation of angiogenin factor in the microvascular endothelial cells, inhibition of MAPK and ERK 1/2 phosphorylation activity. Lastly, A3AR is expressed in low levels in normal cells whereas the expression is upregulated in tumour cells, however, agonists to this receptor inhibit tumour proliferation through modulation of Wnt and NF-κB signaling pathways. Several researchers are in search for potential agents to modulate the overexpressed ARs to control cancer. Active components of A2AAR antagonists and A3AR agonists have already entered in Phase-I clinical research to prove their safety in human. This review focused on novel research targets towards the prevention of cancer progression through stimulation of the overexpressed ARs with the hope to protect lives and advance human health.
    Matched MeSH terms: Adenosine/physiology*
  17. Adenosine Receptors in Modulation of Central Nervous System Disorders
    Choudhury H, Chellappan DK, Sengupta P, Pandey M, Gorain B
    Curr Pharm Des, 2019;25(26):2808-2827.
    PMID: 31309883 DOI: 10.2174/1381612825666190712181955
    The ubiquitous signaling nucleoside molecule, adenosine is found in different cells of the human body to provide its numerous pharmacological role. The associated actions of endogenous adenosine are largely dependent on conformational change of the widely expressed heterodimeric G-protein-coupled A1, A2A, A2B, and A3 adenosine receptors (ARs). These receptors are well conserved on the surface of specific cells, where potent neuromodulatory properties of this bioactive molecule reflected by its easy passage through the rigid blood-brainbarrier, to simultaneously act on the central nervous system (CNS). The minimal concentration of adenosine in body fluids (30-300 nM) is adequate to exert its neuromodulatory action in the CNS, whereas the modulatory effect of adenosine on ARs is the consequence of several neurodegenerative diseases. Modulatory action concerning the activation of such receptors in the CNS could be facilitated towards neuroprotective action against such CNS disorders. Our aim herein is to discuss briefly pathophysiological roles of adenosine on ARs in the modulation of different CNS disorders, which could be focused towards the identification of potential drug targets in recovering accompanying CNS disorders. Researches with active components with AR modulatory action have been extended and already reached to the bedside of the patients through clinical research in the improvement of CNS disorders. Therefore, this review consist of recent findings in literatures concerning the impact of ARs on diverse CNS disease pathways with the possible relevance to neurodegeneration.
    Matched MeSH terms: Adenosine/physiology*
  18. Fulltext Inhibition of Human Platelet Aggregation and Low-Density Lipoprotein Oxidation by Premna foetida Extract and Its Major Compounds
    Dianita R, Jantan I
    Molecules, 2019 Apr 13;24(8).
    PMID: 31013947 DOI: 10.3390/molecules24081469
    Many Premna species have been used in traditional medicine to treat hypertension and cardiac insufficiency, and as a tonic for cardiac-related problems. Some have been reported to possess cardiovascular protective activity through several possible mechanisms, but not Premna foetida. In the present study, the methanol extract of P. foetida leaves (PFM) and its isolated compounds were evaluated for their ability to inhibit copper-mediated human low-density lipoprotein (LDL) oxidation and arachidonic acid (AA)- and adenosine diphosphate (ADP)-induced platelet aggregation. Six flavonoids, three triterpenoids, vanillic acid and stigmasterol were successfully isolated from PFM. Of the isolated compounds, quercetin was the most active against LDL oxidation (IC50 4.25 µM). The flavonols were more active than the flavones against LDL oxidation, suggesting that hydroxyl group at C-3 and the catechol moiety at B-ring may play important roles in protecting LDL from oxidation. Most tested flavonoids showed stronger inhibition towards AA-induced than the ADP-induced platelet aggregation with apigenin exhibiting the strongest effect (IC50 52.3 and 127.4 µM, respectively) while quercetin and kaempferol showed moderate activity. The results suggested that flavonoids, especially quercetin, apigenin and kaempferol were among the major constituents of P. foetida responsible for anti-LDL oxidation and anti-platelet aggregation.
    Matched MeSH terms: Adenosine Diphosphate/pharmacology
  19. Fulltext Role of Purinergic Signalling in Endothelial Dysfunction and Thrombo-Inflammation in Ischaemic Stroke and Cerebral Small Vessel Disease
    Lee NT, Ong LK, Gyawali P, Nassir CMNCM, Mustapha M, Nandurkar HH, et al.
    Biomolecules, 2021 07 06;11(7).
    PMID: 34356618 DOI: 10.3390/biom11070994
    The cerebral endothelium is an active interface between blood and the central nervous system. In addition to being a physical barrier between the blood and the brain, the endothelium also actively regulates metabolic homeostasis, vascular tone and permeability, coagulation, and movement of immune cells. Being part of the blood-brain barrier, endothelial cells of the brain have specialized morphology, physiology, and phenotypes due to their unique microenvironment. Known cardiovascular risk factors facilitate cerebral endothelial dysfunction, leading to impaired vasodilation, an aggravated inflammatory response, as well as increased oxidative stress and vascular proliferation. This culminates in the thrombo-inflammatory response, an underlying cause of ischemic stroke and cerebral small vessel disease (CSVD). These events are further exacerbated when blood flow is returned to the brain after a period of ischemia, a phenomenon termed ischemia-reperfusion injury. Purinergic signaling is an endogenous molecular pathway in which the enzymes CD39 and CD73 catabolize extracellular adenosine triphosphate (eATP) to adenosine. After ischemia and CSVD, eATP is released from dying neurons as a damage molecule, triggering thrombosis and inflammation. In contrast, adenosine is anti-thrombotic, protects against oxidative stress, and suppresses the immune response. Evidently, therapies that promote adenosine generation or boost CD39 activity at the site of endothelial injury have promising benefits in the context of atherothrombotic stroke and can be extended to current CSVD known pathomechanisms. Here, we have reviewed the rationale and benefits of CD39 and CD39 therapies to treat endothelial dysfunction in the brain.
    Matched MeSH terms: Adenosine Triphosphate/metabolism*
  20. Cellular and hormonal control in glycogen metabolism--recent advances
    Thambyrajah V, Karunairatnam MC
    Med J Malaya, 1972 Sep;27(1):33-9.
    PMID: 4345646
    Matched MeSH terms: Adenosine Triphosphate/metabolism
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