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  1 / 5676 MEDLINE  
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PMID:29355013
Autor:Zhang W; Li X; Hua F; Chen W; Wang W; Chu GX; Bao GH
Endereço:Natural Products Laboratory, International Joint Lab of Tea Chemistry and Health Effects, State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University , Hefei, 230036 People's Republic of China.
Título:Interaction between Ester-Type Tea Catechins and Neutrophil Gelatinase-Associated Lipocalin: Inhibitory Mechanism.
Fonte:J Agric Food Chem; 66(5):1147-1156, 2018 Feb 07.
ISSN:1520-5118
País de publicação:United States
Idioma:eng
Resumo:Tea is thought to alleviate neurotoxicity due to the antioxidative effect of ester-type tea catechins (ETC). Neutrophil gelatinase-associated lipocalin (NGAL) can sensitize ß-amyloid (Aß) induced neurotoxicity, and inhibitors of NGAL may relieve associated symptoms. As such, the interactions of ETC with NGAL were investigated by fluorescence spectrometry and molecular simulation. NGAL fluorescence is quenched regularly when being added with six processing types of tea infusion (SPTT) and ETC. Thermodynamic analyses suggest that ETC with more catechol moieties has a stronger binding capacity with NGAL especially in the presence of Fe . (-)-Epicatechin 3-O-caffeoate (ECC), a natural product isolated from Zijuan green tea, shows the strongest binding ability with NGAL (K = 15.21 ± 8.68 nM in the presence of Fe ). All ETC are effective in protecting nerve cells against H O or Aß induced injury. The inhibitory mechanism of ETC against NGAL supports its potential use in attenuation of neurotoxicity.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Esters); 0 (Iron Chelating Agents); 0 (Lipocalin-2); 0 (Neuroprotective Agents); 0 (Tea); 8R1V1STN48 (Catechin); BBX060AN9V (Hydrogen Peroxide)


  2 / 5676 MEDLINE  
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PMID:29333856
Autor:Xie Y; Zhu X; Li Y; Wang C
Endereço:School of Food Science and Technology, Henan University of Technology , Zhengzhou, Henan 450001, People's Republic of China.
Título:Analysis of the pH-Dependent Fe(III) Ion Chelating Activity of Anthocyanin Extracted from Black Soybean [Glycine max (L.) Merr.] Coats.
Fonte:J Agric Food Chem; 66(5):1131-1139, 2018 Feb 07.
ISSN:1520-5118
País de publicação:United States
Idioma:eng
Resumo:The Fe(III) chelating activity of anthocyanin extracted from black soybean coats was investigated at pH 3.0, 5.0, 6.5, 7.0, and 7.4 with fluorescence spectroscopy and microscale thermophoresis (MST). Cyanidin-3-glucoside (C3G) was determined to be 98% of the total anthocyanin by high-performance liquid chromatography. The binding affinity (K ) exhibited significant pH-dependent behavior: K was 9.7167 × 10 , 1.0837 × 10 , 1.4284 × 10 , 5.4550 × 10 , and 3.0269 × 10 M at pH 3.0, 5.0, 6.5, 7.0, and 7.4, respectively (p < 0.05). The MST data showed that ΔG < 0 and ΔH < 0, demonstrating that chelation is spontaneous and exothermic. Because both ΔH and ΔS < 0, the chelation involves hydrogen bonds and/or van der Waals forces for pH 3.0, 5.0, and 6.5. Electrostatic interactions contributed to chelation at pH 7.0 and 7.4 with ΔH < 0 and ΔS > 0. With the formation of chelates, C3G improved the solubility of Fe(III) at pH 6.5, 7.0, and 7.4 to enhance the ferric ion bioavailability, except for aggregation observed at pH 5.0.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Anthocyanins); 0 (Ferric Compounds); 0 (Iron Chelating Agents)


  3 / 5676 MEDLINE  
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PMID:28930516
Autor:Kolnagou A; Kontoghiorghe CN; Kontoghiorghes GJ
Endereço:Postgraduate Research Institute of Science, Technology, Environment and Medicine Limassol, Cyprus, Greece.
Título:New targeted therapies and diagnostic methods for iron overload diseases.
Fonte:Front Biosci (Schol Ed); 10:1-20, 2018 01 01.
ISSN:1945-0524
País de publicação:United States
Idioma:eng
Resumo:Millions of people worldwide suffer from iron overload toxicity diseases such as transfusional iron overload in thalassaemia and hereditary haemochromatosis. The accumulation and presence of toxic focal iron deposits causing tissue damage can also be identified in Friedreich's ataxia, Alzheimer's, Parkinson's, renal and other diseases. Different diagnostic criteria of toxicity and therapeutic interventions apply to each disease of excess or misplaced iron. Magnetic resonance imaging relaxation times T2 and T2* for monitoring iron deposits in organs and iron biomarkers such as serum ferritin and transferrin iron saturation have contributed in the elucidation of iron toxicity mechanisms and pathways, and also the evaluation of the efficacy and mode of action of chelating drugs in the treatment of diseases related to iron overload, toxicity and metabolism. Similarly, histopathological and electron microscopy diagnostic methods have revealed mechanisms of iron overload toxicity at cellular and sub-cellular levels. These new diagnostic criteria and chelator dose adjustments could apply in different or special patient categories e.g. thalassaemia patients with normal iron stores, where iron deficiency and over-chelation toxicity should be avoided.
Tipo de publicação: JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, NON-U.S. GOV'T
Nome de substância:0 (Iron Chelating Agents); E1UOL152H7 (Iron)


  4 / 5676 MEDLINE  
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PMID:29200160
Autor:Gomber S; Dabas A; Bagmar S; Madhu SV
Endereço:Departments of Pediatrics.
Título:Glucose Homeostasis and Effect of Chelation on ß Cell Function in Children With ß-Thalassemia Major.
Fonte:J Pediatr Hematol Oncol; 40(1):56-59, 2018 Jan.
ISSN:1536-3678
País de publicação:United States
Idioma:eng
Resumo:OBJECTIVE: To assess the prevalence of impaired glucose tolerance in ß-thalassemia major and correlate it with chelation therapy. MATERIALS AND METHODS: Sixty-seven subjects with ß-thalassemia major, aged 1 to 20 years, were enrolled in our prospective cohort. Clinical details were recorded. Baseline oral glucose tolerance test, serum insulin, C peptide, and insulin resistance were measured. The biochemical profile was repeated after 6 months. RESULTS: The mean age of subjects was 7.43±4.48 years. Eight (11.9%) subjects had impaired fasting glucose, 7 (10.4%) had impaired glucose tolerance, and 1 (1.4%) subject had diabetes at baseline. Subjects with abnormal glucose profile had longer disease duration (95% confidence interval [CI] of difference=-6.64 to -0.68; P=0.019) and higher fasting blood glucose (95% CI of difference=-32.1 to -10.5; P=0.001) and serum ferritin (95% CI of difference=-219.8 to -3.4; P=0.001) than normoglycemic subjects. Insulin resistance and serum ferritin showed significant increase at 6 months (P<0.001 and P=0.001, respectively). Patients on deferiprone alone significantly improved glucose homeostasis on follow-up than those on desferrioxamine or combination therapy of desferrioxamine and deferiprone (P<0.05). CONCLUSIONS: Prolonged disease duration and higher serum ferritin adversely affects glucose homeostasis in thalassemic children. Deferiprone was the most effective chelator to improve glucose homeostasis in chronically transfused thalassemics.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Blood Glucose); 0 (Iron Chelating Agents); 0 (Pyridones); 2BTY8KH53L (deferiprone); 9007-73-2 (Ferritins); J06Y7MXW4D (Deferoxamine)


  5 / 5676 MEDLINE  
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Carvalho, Denise P
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PMID:29180001
Autor:Bernardes JR; Faria CC; Andrade IS; Ferreira ACF; Carvalho DP; Leitão AC; de Alencar TAM; Fortunato RS
Endereço:Laboratório de Radiobiologia Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Título:Effect of the FE chelation by 2,2'-dipyridyl in the doxorubicin-induced lethality in breast tumor cell lines.
Fonte:Life Sci; 192:128-135, 2018 Jan 01.
ISSN:1879-0631
País de publicação:Netherlands
Idioma:eng
Resumo:Breast cancer cells may exhibit changes in iron homeostasis, which results in increased labile iron pool (LIP) levels. Several studies highlight the crucial role of high LIP levels in the maintenance of tumor cell physiology. Iron chelators have been tested in anticancer therapy in combination with chemotherapeutic agents, to improve drug efficacy. Thus, the aim of this study was to evaluate the effect of 2,2'-dipyridyl (DIP), a Fe chelator, in combination with doxorubicin (DOX) in breast tumor cells. The maximum concentration of DIP that did not significantly reduce the viability of MDA-MB-231 cells was 10µM and for MCF-7 cells was 50µM. We observed that MCF-7 had higher LIP levels than MDA-MB-231 cells. DIP alone increased ROS generation in MCF-7 cells, and DIP pretreatment reduced ROS generation induced by DOX treatment. In conclusion, the increase in MCF-7 cell viability induced by DIP pretreatment in DOX-treated cells seems to be related to an increase in the cellular antioxidant capacity and the iron chelator did not improve drug efficacy in the two breast tumor cell lines analyzed.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Antibiotics, Antineoplastic); 0 (Iron Chelating Agents); 0 (RNA, Messenger); 0 (Reactive Oxygen Species); 551W113ZEP (2,2'-Dipyridyl); 80168379AG (Doxorubicin); EC 1.6.3.- (NADPH Oxidases)


  6 / 5676 MEDLINE  
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PMID:29200434
Autor:Ahlgren EC; Fekry M; Wiemann M; Söderberg CA; Bernfur K; Gakh O; Rasmussen M; Højrup P; Emanuelsson C; Isaya G; Al-Karadaghi S
Endereço:Center for Molecular Protein Science, Department of Biochemistry and Structural Biology, Lund University, Lund, Sweden.
Título:Iron-induced oligomerization of human FXN81-210 and bacterial CyaY frataxin and the effect of iron chelators.
Fonte:PLoS One; 12(12):e0188937, 2017.
ISSN:1932-6203
País de publicação:United States
Idioma:eng
Resumo:Patients suffering from the progressive neurodegenerative disease Friedreich's ataxia have reduced expression levels of the protein frataxin. Three major isoforms of human frataxin have been identified, FXN42-210, FXN56-210 and FXN81-210, of which FXN81-210 is considered to be the mature form. Both long forms, FXN42-210 and FXN56-210, have been shown to spontaneously form oligomeric particles stabilized by the extended N-terminal sequence. The short variant FXN81-210, on other hand, has only been observed in the monomeric state. However, a highly homologous E. coli frataxin CyaY, which also lacks an N-terminal extension, has been shown to oligomerize in the presence of iron. To explore the mechanisms of stabilization of short variant frataxin oligomers we compare here the effect of iron on the oligomerization of CyaY and FXN81-210. Using dynamic light scattering, small-angle X-ray scattering, electron microscopy (EM) and cross linking mass spectrometry (MS), we show that at aerobic conditions in the presence of iron both FXN81-210 and CyaY form oligomers. However, while CyaY oligomers are stable over time, FXN81-210 oligomers are unstable and dissociate into monomers after about 24 h. EM and MS studies suggest that within the oligomers FXN81-210 and CyaY monomers are packed in a head-to-tail fashion in ring-shaped structures with potential iron-binding sites located at the interface between monomers. The higher stability of CyaY oligomers can be explained by a higher number of acidic residues at the interface between monomers, which may result in a more stable iron binding. We also show that CyaY oligomers may be dissociated by ferric iron chelators deferiprone and DFO, as well as by the ferrous iron chelator BIPY. Surprisingly, deferiprone and DFO stimulate FXN81-210 oligomerization, while BIPY does not show any effect on oligomerization in this case. The results suggest that FXN81-210 oligomerization is primarily driven by ferric iron, while both ferric and ferrous iron participate in CyaY oligomer stabilization. Analysis of the amino acid sequences of bacterial and eukaryotic frataxins suggests that variations in the position of the acidic residues in helix 1, ß-strand 1 and the loop between them may control the mode of frataxin oligomerization.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Cross-Linking Reagents); 0 (Escherichia coli Proteins); 0 (Iron Chelating Agents); 0 (Iron-Binding Proteins); 0 (Protein Isoforms); 0 (Recombinant Proteins); 0 (frataxin); E1UOL152H7 (Iron)


  7 / 5676 MEDLINE  
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PMID:28741691
Autor:Origa R; Tatti F; Zappu A; Leoni GB; Dessì C; Moi P; Morittu M; Orecchia V; Denotti AR; Pilia MP; Anni F; Perra M; Casini MR; Barella S
Endereço:Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
Título:Earlier initiation of transfusional and iron chelation therapies in recently born children with transfusion-dependent thalassemia.
Fonte:Am J Hematol; 92(11):E627-E628, 2017 Nov.
ISSN:1096-8652
País de publicação:United States
Idioma:eng
Tipo de publicação: LETTER
Nome de substância:0 (Iron Chelating Agents)


  8 / 5676 MEDLINE  
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PMID:29049732
Autor:Wang K; Peng B; Xiao J; Weinreb O; Youdim MBH; Lin B
Endereço:Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, China.
Título:Iron-Chelating Drugs Enhance Cone Photoreceptor Survival in a Mouse Model of Retinitis Pigmentosa.
Fonte:Invest Ophthalmol Vis Sci; 58(12):5287-5297, 2017 Oct 01.
ISSN:1552-5783
País de publicação:United States
Idioma:eng
Resumo:Purpose: Retinitis pigmentosa (RP) is a group of hereditary retinal degeneration in which mutations commonly result in the initial phase of rod cell death followed by gradual cone cell death. The mechanisms by which the mutations lead to photoreceptor cell death in RP have not been clearly elucidated. There is currently no effective treatment for RP. The purpose of this work was to explore iron chelation therapy for improving cone survival and function in the rd10 mouse model of RP. Methods: Two iron-chelating drugs, 5-(4-(2-hydroxyethyl) piperazin-1-yl (methyl)-8-hydroxyquinoline (VK28) and its chimeric derivative 5-(N-methyl-N-propargyaminomethyl)-quinoline-8-oldihydrochloride (VAR10303), were injected intraperitoneally to rd10 mice every other day starting from postnatal day 14. We investigate the effects of the two compounds on cone rescue at three time points, using a combination of immunocytochemistry, RT-PCR, Western blot analysis, and a series of visual function tests. Results: VK28 and VAR10303 treatments partially rescued cones, and significantly improved visual function in rd10 mice. Moreover, we showed that the neuroprotective effects of VK28 and VAR10303 were correlated to inhibition of neuroinflammation, oxidative stress, and apoptosis. Furthermore, we demonstrated that downregulation of NF-kB and p53 is likely to be the mechanisms by which proinflammatory mediators and apoptosis are reduced in the rd10 retina, respectively. Conclusions: VK28 and VAR10303 provided partial histologic and functional rescue of cones in RD10 mice. Our study demonstrated that iron chelation therapy might represent an effective therapeutic strategy for RP patients.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (5-(2-(methylprop-2-ynylamino)ethyl)quinolin-8-ol); 0 (5-(4-(2-hydroxyethyl)piperazine-1-ylmethyl)quinoline-8-ol); 0 (Hydroxyquinolines); 0 (Iron Chelating Agents); 0 (NF-kappa B); 0 (Neuroprotective Agents); 0 (Piperazines); 0 (Quinolines); 0 (Tumor Suppressor Protein p53)


  9 / 5676 MEDLINE  
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PMID:28953994
Autor:Dias-Lopes G; Saboia-Vahia L; Margotti ET; Fernandes NS; Castro CLF; Oliveira FO; Peixoto JF; Britto C; Silva FCE; Cuervo P; Jesus JB
Endereço:Fundação Oswaldo Cruz-Fiocruz, Instituto Oswaldo Cruz, Laboratório de Biologia Molecular e Doenças Endêmicas, Rio de Janeiro, RJ, Brasil.
Título:Morphologic study of the effect of iron on pseudocyst formation in Trichomonas vaginalis and its interaction with human epithelial cells.
Fonte:Mem Inst Oswaldo Cruz; 112(10):664-673, 2017 Oct.
ISSN:1678-8060
País de publicação:Brazil
Idioma:eng
Resumo:BACKGROUND: Trichomonas vaginalis is the aetiological agent of human trichomoniasis, which is one of the most prevalent sexually transmitted diseases in humans. Iron is an important element for the survival of this parasite and the colonisation of the host urogenital tract. OBJECTIVES: In this study, we investigated the effects of iron on parasite proliferation in the dynamics of pseudocyst formation and morphologically characterised iron depletion-induced pseudocysts. METHODS: We performed structural and ultrastructural analyses using light microscopy, scanning electron microscopy and transmission electron microscopy. FINDINGS: It was observed that iron depletion (i) interrupts the proliferation of T. vaginalis, (ii) induces morphological changes in typical multiplicative trophozoites to spherical non-proliferative, non-motile pseudocysts, and (iii) induces the arrest of cell division at different stages of the cell cycle; (iv) iron is the fundamental element for the maintenance of typical trophozoite morphology; (v) pseudocysts induced by iron depletion are viable and reversible forms; and, finally, (vi) we demonstrated that pseudocysts induced by iron depletion are able to interact with human epithelial cells maintaining their spherical forms. MAIN CONCLUSIONS: Together, these data suggest that pseudocysts could be induced as a response to iron nutritional stress and could have a potential role in the transmission and infection of T. vaginalis.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Iron Chelating Agents)


  10 / 5676 MEDLINE  
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PMID:28884221
Autor:Klonizakis P; Klaassen R; Sousos N; Liakos A; Tsapas A; Vlachaki E
Endereço:Adults Thalassemia Unit, 2nd Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital of Thessaloniki, 49, Konstantinoupoleos Street, 54642, Thessaloniki, Greece. philklon@gmail.com.
Título:Evaluation of the Greek TranQol: a novel questionnaire for measuring quality of life in transfusion-dependent thalassemia patients.
Fonte:Ann Hematol; 96(11):1937-1944, 2017 Nov.
ISSN:1432-0584
País de publicação:Germany
Idioma:eng
Resumo:The aim of our study was to evaluate the Greek version of the transfusion-dependent quality of life (TranQol) questionnaire and report our experience of using this novel disease-specific quality of life (QoL) measure in patients with transfusion-dependent thalassemia (TDT). The TranQol and SF-36v2 questionnaires were administered to 94 adult TDT patients with a mean age of 32.1 years (SD = 7, range = 19-58), recruited from the Adult Thalassemia Unit of Hippokration General Hospital of Thessaloniki, Greece. The TranQol was evaluated in terms of construct validity, reliability, and responsiveness. There was a moderately strong correlation between the TranQol summary and both the SF-36v2 physical and mental component summaries (r = 0.4, p < 0.001 and r = 0.5, p < 0.001, respectively). There was also a moderately strong correlation between the physical health scale of TranQol and the relevant SF-36v2 scales, including physical functioning (r = 0.4, p < 0.001), role-physical (r = 0.6, p < 0.001), and bodily pain (r = 0.5, p < 0.001). TranQol also exhibited good internal consistency (Cronbach's alpha coefficient = 0.9) and excellent test-retest reliability (intra-class correlation coefficient = 0.9). The subgroup of patients that reported a better QoL 1 week after transfusion also demonstrated a significant improvement in their TranQol score. These are the first data regarding the administration of the Greek TranQol in a single thalassemia unit. The psychometric properties of the Greek TranQol confirmed it is a valid, reliable, and responsive to change questionnaire, which can be incorporated into future clinical trials.
Tipo de publicação: JOURNAL ARTICLE; OBSERVATIONAL STUDY
Nome de substância:0 (Iron Chelating Agents)



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