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Search on : adenosine and deaminase [Words]
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[PMID]: 29522447
[Au] Autor:Camici M; Garcia-Gil M; Tozzi MG
[Ad] Address:Dipartimento di Biologia, Unità di Biochimica, Via San Zeno 51, 56127 Pisa, Italy. marcella.camici@unipi.it.
[Ti] Title:The Inside Story of Adenosine.
[So] Source:Int J Mol Sci;19(3), 2018 Mar 09.
[Is] ISSN:1422-0067
[Cp] Country of publication:Switzerland
[La] Language:eng
[Ab] Abstract:Several physiological functions of adenosine (Ado) appear to be mediated by four G protein-coupled Ado receptors. Ado is produced extracellularly from the catabolism of the excreted ATP, or intracellularly from AMP, and then released through its transporter. High level of intracellular Ado occurs only at low energy charge, as an intermediate of ATP breakdown, leading to hypoxanthine production. AMP, the direct precursor of Ado, is now considered as an important stress signal inside cell triggering metabolic regulation through activation of a specific AMP-dependent protein kinase. Intracellular Ado produced from AMP by allosterically regulated nucleotidases can be regarded as a stress signal as well. To study the receptor-independent effects of Ado, several experimental approaches have been proposed, such as inhibition or silencing of key enzymes of Ado metabolism, knockdown of Ado receptors in animals, the use of antagonists, or cell treatment with deoxyadenosine, which is substrate of the enzymes acting on Ado, but is unable to interact with Ado receptors. In this way, it was demonstrated that, among other functions, intracellular Ado modulates angiogenesis by regulating promoter methylation, induces hypothermia, promotes apoptosis in sympathetic neurons, and, in the case of oxygen and glucose deprivation, exerts a cytoprotective effect by replenishing the ATP pool.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1803
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Process

  2 / 13061 MEDLINE  
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[PMID]: 29433935
[Au] Autor:Cicalese MP; Ferrua F; Castagnaro L; Rolfe K; De Boever E; Reinhardt RR; Appleby J; Roncarolo MG; Aiuti A
[Ad] Address:San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy, 20132; Pediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy, 20132.
[Ti] Title:Gene Therapy for Adenosine Deaminase Deficiency: A Comprehensive Evaluation of Short- and Medium-Term Safety.
[So] Source:Mol Ther;26(3):917-931, 2018 Mar 07.
[Is] ISSN:1525-0024
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Loss of adenosine deaminase activity leads to severe combined immunodeficiency (ADA-SCID); production and function of T, B, and natural killer (NK) cells are impaired. Gene therapy (GT) with an autologous CD34 -enriched cell fraction that contains CD34 cells transduced with a retroviral vector encoding the human ADA cDNA sequence leads to immune reconstitution in most patients. Here, we report short- and medium-term safety analyses from 18 patients enrolled as part of single-arm, open-label studies or compassionate use programs. Survival was 100% with a median of 6.9 years follow-up (range, 2.3 to 13.4 years). Adverse events were mostly grade 1 or grade 2 and were reported by all 18 patients following GT. Thirty-nine serious adverse events (SAEs) were reported by 15 of 18 patients; no SAEs were considered related to GT. The most common adverse events reported post-GT include upper respiratory tract infection, gastroenteritis, rhinitis, bronchitis, oral candidiasis, cough, neutropenia, diarrhea, and pyrexia. Incidence rates for all of these events were highest during pre-treatment, treatment, and/or 3-month follow-up and then declined over medium-term follow-up. GT did not impact the incidence of neurologic/hearing impairments. No event indicative of leukemic transformation was reported.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:In-Data-Review

  3 / 13061 MEDLINE  
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[PMID]: 29411230
[Au] Autor:Michniacki TF; Hannibal M; Ross CW; Frame DG; DuVall AS; Khoriaty R; Vander Lugt MT; Walkovich KJ
[Ad] Address:Pediatrics and Communicable Diseases, Pediatric Hematology/Oncology, University of Michigan, 1500 E. Medical Center Drive, D4202 Medical Professional Building, Ann Arbor, MI, 48109, USA. tmich@med.umich.edu.
[Ti] Title:Hematologic Manifestations of Deficiency of Adenosine Deaminase 2 (DADA2) and Response to Tumor Necrosis Factor Inhibition in DADA2-Associated Bone Marrow Failure.
[So] Source:J Clin Immunol;38(2):166-173, 2018 Feb.
[Is] ISSN:1573-2592
[Cp] Country of publication:Netherlands
[La] Language:eng
[Pt] Publication type:LETTER
[Em] Entry month:1802
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Data-Review
[do] DOI:10.1007/s10875-018-0480-4

  4 / 13061 MEDLINE  
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[PMID]: 29172693
[Au] Autor:Ojeda-Montes MJ; Ardid-Ruiz A; Tomás-Hernández S; Gimeno A; Cereto-Massagué A; Beltrán-Debón R; Mulero M; Garcia-Vallvé S; Pujadas G; Valls C
[Ad] Address:Research group in Cheminformatics & Nutrition, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Campus de Sescelades, Tarragona, Catalonia 43007, Spain.
[Ti] Title:Ephedrine as a lead compound for the development of new DPP-IV inhibitors.
[So] Source:Future Med Chem;9(18):2129-2146, 2017 12.
[Is] ISSN:1756-8927
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:AIM: Extracts from Ephedra species have been reported to be effective as antidiabetics. A previous in silico study predicted that ephedrine and five ephedrine derivatives could contribute to the described antidiabetic effect of Ephedra extracts by inhibiting dipeptidyl peptidase IV (DPP-IV). Finding selective DPP-IV inhibitors is a current therapeutic strategy for Type 2 diabetes mellitus management. Therefore, the main aim of this work is to experimentally determine whether these alkaloids are DPP-IV inhibitors. Materials & methods: The DPP-IV inhibition of Ephedra's alkaloids was determined via a competitive-binding assay. Then, computational analyses were used in order to find out the protein-ligand interactions and to perform a lead optimization. RESULTS: Our results show that all six molecules are DPP-IV inhibitors, with IC ranging from 124 µM for ephedrine to 28 mM for N-methylpseudoephedrine. CONCLUSION: Further computational analysis shows how Ephedra's alkaloids could be used as promising lead molecules for designing more potent and selective DPP-IV inhibitors.
[Mh] MeSH terms primary: Dipeptidyl Peptidase 4/metabolism
Dipeptidyl-Peptidase IV Inhibitors/chemistry
Ephedrine/analogs & derivatives
Hypoglycemic Agents/chemistry
[Mh] MeSH terms secundary: Alkaloids/chemistry
Alkaloids/metabolism
Binding Sites
Binding, Competitive
Dipeptidyl Peptidase 4/chemistry
Drug Design
Ephedra/chemistry
Ephedra/metabolism
Ephedrine/metabolism
Hypoglycemic Agents/metabolism
Inhibitory Concentration 50
Molecular Docking Simulation
Phenylpropanolamine/chemistry
Plant Extracts/chemistry
Protein Isoforms/antagonists & inhibitors
Protein Isoforms/metabolism
Protein Structure, Tertiary
Stereoisomerism
Structure-Activity Relationship
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Alkaloids); 0 (Dipeptidyl-Peptidase IV Inhibitors); 0 (Hypoglycemic Agents); 0 (Plant Extracts); 0 (Protein Isoforms); 33RU150WUN (Phenylpropanolamine); EC 3.4.14.5 (Dipeptidyl Peptidase 4); GN83C131XS (Ephedrine)
[Em] Entry month:1712
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[Js] Journal subset:IM
[Da] Date of entry for processing:171128
[St] Status:MEDLINE
[do] DOI:10.4155/fmc-2017-0080

  5 / 13061 MEDLINE  
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[PMID]: 29446860
[Au] Autor:Solari L; Soto A; Van der Stuyft P
[Ad] Address:Unit of General Epidemiology and Disease Control, Institute of Tropical Medicine of Antwerp, Antwerp, Belgium.
[Ti] Title:Development of a clinical prediction rule for tuberculous meningitis in adults in Lima, Peru.
[So] Source:Trop Med Int Health;, 2018 Feb 15.
[Is] ISSN:1365-3156
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:OBJECTIVES: Diagnosis of tuberculous meningitis (TM) is a challenge in countries with a high burden of the disease and constrained resources and clinical prediction rules (CPRs) could be of assistance. We aimed at developing a CPR for diagnosis of TM in a Latin American setting with high tuberculosis incidence and a concentrated HIV epidemic. METHODS: We enrolled adult patients with clinical suspicion of TM attending two hospitals in Lima, Peru. We obtained information on potential anamnestic, clinical and laboratory predictive findings that are easy to collect and promptly available. We independently diagnosed TM according to a composite reference standard that included a series of microbiological tests. We performed bivariate analysis and constructed a logistic regression model to select the predictive findings associated with TM. With the selected predictors included in the model, we developed a score-based CPR. We assessed its internal validity and diagnostic performance. RESULTS: Of 155 analysed patients, 59 (38%) had TM. The CPR we derived includes three predictors: cough for 14 days or more, 10-500 cells in CSF and adenosine deaminase ≥ 6 U/l in CSF. It classifies patients into high-, moderate- or low-score groups and has an overall area under the ROC curve of 0.87. 59% of patients were assigned to either the high- or the low-score group, permitting prompt decision-making. In patients in the high-score group, it attains a positive likelihood ratio for TM of 10.6 and in patients with low scores, a negative likelihood ratio of 0.10. Bootstrap analysis indicated high internal validity. CONCLUSION: This CPR could support decision-making in patients with clinical suspicion of TM. External validation and further assessment of its clinical impact are necessary before application in other settings.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:Publisher
[do] DOI:10.1111/tmi.13041

  6 / 13061 MEDLINE  
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[PMID]: 28453746
[Au] Autor:Zhu C; Mustafa D; Zheng PP; van der Weiden M; Sacchetti A; Brandt M; Chrifi I; Tempel D; Leenen PJM; Duncker DJ; Cheng C; Kros JM
[Ad] Address:Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands.
[Ti] Title:Activation of CECR1 in M2-like TAMs promotes paracrine stimulation-mediated glial tumor progression.
[So] Source:Neuro Oncol;19(5):648-659, 2017 05 01.
[Is] ISSN:1523-5866
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Background: The majority of glioma-associated microglia/macrophages have been identified as M2-type macrophages with immune suppressive and tumor supportive action. Recently, the extracellular adenosine deaminase protein Cat Eye Syndrome Critical Region Protein 1 (CECR1) was shown to regulate macrophage maturation. In this study, we investigate the role of CECR1 in the regulation of the glioma-associated macrophage response. Methods: Expression of CECR1 was assessed in human glioma samples. CECR1-mediated macrophage response was studied in vitro, using donor derived CD14+ monocytes and the THP-1 monocytic cell line. The response of the human glioma cell line U87 to conditioned medium of macrophages preconditioned with recombinant human CECR1 or CECR1 silencing was also assessed. Results: CECR1 was strongly expressed in high-grade gliomas (P < .001) and correlated positively with the M2 phenotype markers in tumor-associated microglia/macrophages (TAMs) (overall, P < .05). In vitro studies confirmed the presence of a significantly higher level of CECR1 expression in M2-like macrophages exposed to U87 conditioned medium (P < .001). CECR1 knockdown or stimulation of macrophages affected differentiation toward the M2-like phenotype. Stimulation of U87 cells with conditioned medium of CECR1 knockdown or stimulated macrophages affected tumor cell proliferation and migration, coinciding with altered intracellular signaling of mitogen-activated protein kinase (MAPK). In glioma tissue samples, CECR1 expression correlated with Ki67 and MAPK signaling protein. Conclusions: CECR1 is a potent regulator of TAM polarization and is consistently highly expressed by M2-type TAMs, particularly in high-grade glioma. Paracrine effects induced by CECR1 in M2-like TAMs activate MAPK signaling and stimulate the proliferation and migration of glioma cells.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1704
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[St] Status:In-Process
[do] DOI:10.1093/neuonc/now251

  7 / 13061 MEDLINE  
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[PMID]: 29374928
[Au] Autor:Song CL; Yao M
[Ad] Address:Department of Plastic Surgery and Burns, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201900, China.
[Ti] Title:[Advances in the research of relationship between CD26 and hypertrophic scar and keloid].
[So] Source:Zhonghua Shao Shang Za Zhi;34(1):54-56, 2018 Jan 20.
[Is] ISSN:1009-2587
[Cp] Country of publication:China
[La] Language:chi
[Ab] Abstract:In recent years, researchers have found that CD26 (dipeptidyl peptidase 4) is closely related to the formation and development of many fibrotic diseases. Hypertrophic scar, keloid, and other skin fibrosis diseases are major problems nowadays, which may affect the patient's appearance and cause joints deformity and dysfunction due to scar contracture. This article briefly reviews the relationship between CD26 and hypertrophic scar and keloid to provide new insights into the treatment of skin fibrotic diseases.
[Mh] MeSH terms primary: Cicatrix, Hypertrophic/pathology
Dipeptidyl Peptidase 4/metabolism
Keloid/pathology
[Mh] MeSH terms secundary: Fibrosis
Humans
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Nm] Name of substance:EC 3.4.14.5 (DPP4 protein, human); EC 3.4.14.5 (Dipeptidyl Peptidase 4)
[Em] Entry month:1803
[Cu] Class update date: 180306
[Lr] Last revision date:180306
[Js] Journal subset:IM
[Da] Date of entry for processing:180129
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.1009-2587.2018.01.011

  8 / 13061 MEDLINE  
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[PMID]: 29506637
[Au] Autor:Fattahi S; Ghadami E; Asouri M; Motevalizadeh Ardekanid A; Akhavan-Niaki H
[Ad] Address:Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
[Ti] Title:Urtica dioica inhibits cell growth and induces apoptosis by targeting Ornithine decarboxylase and Adenosine deaminase as key regulatory enzymes in adenosine and polyamines homeostasis in human breast cancer cell lines.
[So] Source:Cell Mol Biol (Noisy-le-grand);64(3):97-102, 2018 Feb 28.
[Is] ISSN:1165-158X
[Cp] Country of publication:France
[La] Language:eng
[Ab] Abstract:Breast cancer is a heterogeneous and multifactorial disease with variable disease progression risk, and treatment response. Urtica dioica is a traditional herb used as an adjuvant therapeutic agent in cancer. In the present study, we have evaluated the effects of the aqueous extract of Urtica dioica on Adenosine deaminase (ADA) and Ornithine decarboxylase (ODC1) gene expression in MCF-7, MDA-MB-231, two breast cancer cell lines being estrogen receptor positive and estrogen receptor negative, respectively.  Cell lines were cultured in suitable media. After 24 h, different concentrations of the extract were added and after 72 h, ADA and ODC1 gene expression as well as BCL2 and BAX apoptotic genes were assessed by Taqman real time PCR assay. Cells viability was assessed by MTT assay, and apoptosis was also evaluated at cellular level. The intra and extracellular levels of ODC1 and ADA enzymes were evaluated by ELISA. Results showed differential expression of ADA and ODC1 genes in cancer cell lines. In MCF-7 cell line, the expression level of ADA was upregulated in a dose-dependent manner but its expression did not change in MDA-MB cell line. ODC1 expression was increased in both examined cell lines. Also, increased level of the apoptotic BAX/BCL-2 ratio was detected in MCF-7 cells. These results demonstrated that Urtica dioica induces apoptosis in breast cancer cells by influencing ODC1 and ADA genes expression, and estrogen receptors. The different responses observed with these cell lines could be due to the interaction of Urtica dioica as a phytoestrogen with the estrogen receptor.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180306
[Lr] Last revision date:180306
[St] Status:In-Process
[do] DOI:10.14715/cmb/2018.64.3.16

  9 / 13061 MEDLINE  
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[PMID]: 29253595
[Au] Autor:Baldissera MD; Souza CF; Verdi CM; Vizzotto BS; Santos RCV; Baldisserotto B
[Ad] Address:Department of Microbiology and Parasitology, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil. Electronic address: mdbaldissera@mail.ufsm.br.
[Ti] Title:Aeromonas caviae alters the activities of ecto-enzymes that hydrolyze adenine nucleotides in fish thrombocytes.
[So] Source:Microb Pathog;115:64-67, 2017 Dec 16.
[Is] ISSN:1096-1208
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:It is recognized that the purinergic system, through the activities of ectonucleoside triphosphate diphosphohydrolase (E-NTPDase), ecto-5'-nucleotidase (E-5'-nucleotidase), and ecto-adenosine deaminase (E-ADA), is involved in the regulation and modulation of the physiological and pathological events linked to hemostasis. This occurs due to the role of adenosine diphosphate (ADP) in the activation and recruitment of platelets, and the role of adenosine (Ado) in the inhibition of platelet activation. Thus, here we aimed to evaluate whether Aeromonas caviae infection impairs the ecto-enzymes of the purinergic system in fish thrombocytes and the involvement of this system in the hemorrhagic septicemia. The total number of fish thrombocytes decreased in infected animals compared to uninfected animals. Regarding the ecto-enzymes of the purinergic system, the E-NTPDase and E-5'-nucleotidase activities increased in infected animals compared to uninfected animals, while the E-ADA activity decreased. These findings show that adenine nucleotide hydrolysis is modified in the thrombocytes of fish experimentally infected with A. caviae, which impairs the coagulation process due the excessive hydrolysis of ADP, a molecule linked with activation and recruitment of thrombocytes at the site of vascular injury, and augmentation on Ado levels, a molecule linked with inhibitory effects on platelet activation and aggregation. In summary, the purinergic system might contribute to the occurrence of hemorrhagic frames in fish infected with A. caviae.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 180303
[Lr] Last revision date:180303
[St] Status:Publisher

  10 / 13061 MEDLINE  
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[PMID]: 29499460
[Au] Autor:Qi S; Guan H; Deng G; Yang T; Cheng X; Liu W; Liu P; Wang C
[Ad] Address:Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, 1200 Cailun Rood, Shanghai 201203, China.
[Ti] Title:Rapid, reliable, and sensitive detection of adenosine deaminase activity by UHPLC-Q-Orbitrap HRMS and its application to inhibitory activity evaluation of traditional Chinese medicines.
[So] Source:J Pharm Biomed Anal;153:175-181, 2018 Feb 22.
[Is] ISSN:1873-264X
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Adenosine deaminase (ADA), which is a key enzyme in the metabolism of purine nucleosides, plays important roles in diverse disorders, such as tuberculosis, diabetes, liver disorders, and cancer. Determination of the activities of ADA and its isoenzymes in body fluids has received considerable attention in the diagnosis and treatment of relative diseases. Ultraviolet spectroscopy with adenosine (AD) as a substrate is a classical approach for screening potential ADA inhibitors by measuring the decrease in substrate (AD) at 265 nm or increase in the product (inosine) at 248 nm. However, AD and inosine share a very close maximum absorption wavelength, and the reaction is uncertain and is frequently interfered by the background color of matrix compounds or plant extracts. Thus, the method usually yields false positive or negative results. In this study, a novel, rapid, sensitive, and accurate ultra-high-performance liquid chromatography-Q exactive hybrid quadrupole orbitrap high-resolution accurate mass spectrometric (UHPLC-Q-Orbitrap HRMS) method was developed for determining and screening ADA inhibitors by directly determining the deamination product of AD, inosine. A proper separation was achieved for inosine and chlormequat (internal standard) within 2 min via isocratic elution (0.1% formic acid:methanol = 85:15, v/v) at a flow rate of 0.3 mL min on a Waters ACQUITY HSS T3 column (2.1 mm × 100 mm, 1.8 µm) following a simple precipitation of proteins. The intra- and inter-day precisions of the developed method were below 7.17% and 8.99%, respectively. The method exhibited advantages of small total reaction volume (60 µL), short running time (2 min), high sensitivity (lowest limit of quantification of 0.02 µM for inosine), and low cost (small enzyme consumption of 0.007 unit mL for ADA and substrate of 3.74 µM for AD in individual inhibition), and no matrix effects (101.64%-107.12%). Stability results showed that all analytes were stable under the investigated conditions. The developed method was successfully applied to the detection of the inhibitory activity of ADA from traditional Chinese medicines.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180302
[Lr] Last revision date:180302
[St] Status:Publisher


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