Base de dados : MEDLINE
Pesquisa : B01.650.940.800.575.912.250.100.065 [Categoria DeCS]
Referências encontradas : 465 [refinar]
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[PMID]:28863191
[Au] Autor:Sotillo WS; Villagomez R; Smiljanic S; Huang X; Malakpour A; Kempengren S; Rodrigo G; Almanza G; Sterner O; Oredsson S
[Ad] Endereço:Department of Biology, Lund University, Lund, Sweden.
[Ti] Título:Anti-cancer stem cell activity of a sesquiterpene lactone isolated from Ambrosia arborescens and of a synthetic derivative.
[So] Source:PLoS One;12(9):e0184304, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:New regimens are constantly being pursued in cancer treatment, especially in the context of treatment-resistant cancer stem cells (CSCs) that are assumed to be involved in cancer recurrence. Here, we investigated the anti-cancer activity of sesquiterpene lactones (SLs) isolated from Ambrosia arborescens and of synthetic derivatives in breast cancer cell lines, with a specific focus on activity against CSCs. The breast cancer cell lines MCF-7, JIMT-1, and HCC1937 and the normal-like breast epithelial cell line MCF-10A were treated with the SLs damsin and coronopilin, isolated from A. arborescens, and with ambrosin and dindol-01, synthesized using damsin. Inhibitory concentration 50 (IC50) values were obtained from dose-response curves. Based on IC50 values, doses in the µM range were used for investigating effects on cell proliferation, cell cycle phase distribution, cell death, micronuclei formation, and cell migration. Western blot analysis was used to investigate proteins involved in cell cycle regulation as well as in the NF-κB pathway since SLs have been shown to inhibit this transcription factor. Specific CSC effects were investigated using three CSC assays. All compounds inhibited cell proliferation; however, damsin and ambrosin were toxic at single-digit micromolar ranges, while higher concentrations were required for coronopilin and dindol-01. Of the four cell lines, the compounds had the least effect on the normal-like MCF-10A cells. The inhibition of cell proliferation can partly be explained by downregulation of cyclin-dependent kinase 2. All compounds inhibited tumour necrosis factor-α-induced translocation of NF-κB from the cytoplasm to the nucleus. Damsin and ambrosin treatment increased the number of micronuclei; moreover, another sign of DNA damage was the increased level of p53. Treatment with damsin and ambrosin decreased the CSC subpopulation and inhibited cell migration. Our results suggest that these compounds should be further investigated to find efficient CSC-inhibiting compounds.
[Mh] Termos MeSH primário: Ambrosia/química
Antineoplásicos/farmacologia
Lactonas/farmacologia
Células-Tronco Neoplásicas/efeitos dos fármacos
Extratos Vegetais/farmacologia
Sesquiterpenos/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/isolamento & purificação
Azulenos/isolamento & purificação
Azulenos/farmacologia
Ciclo Celular
Linhagem Celular Tumoral
Núcleo Celular/metabolismo
Proliferação Celular/efeitos dos fármacos
Citoplasma/metabolismo
Relação Dose-Resposta a Droga
Seres Humanos
Concentração Inibidora 50
Lactonas/isolamento & purificação
Células MCF-7
Testes para Micronúcleos
NF-kappa B/metabolismo
Células-Tronco Neoplásicas/patologia
Sesquiterpenos/isolamento & purificação
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Azulenes); 0 (Lactones); 0 (NF-kappa B); 0 (Plant Extracts); 0 (Sesquiterpenes); 0 (Tumor Necrosis Factor-alpha); 1216-42-8 (damsin); 6XI048644B (ambrosin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170902
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184304


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[PMID]:28628023
[Au] Autor:Macharadze D; Janaeva H; Avilov K
[Ad] Endereço:1Рeoples Friendship University of Russia, Moscow; 2Janaeva Ch.A., Medical Center, Urus-Martan, Chechnya (Russia); 3Avilov K.K., Institute for Numerical Mathematics of Russian Academy of Sciences, Moscow; 4Federal Research Institute for Health Organization and Informatics of Ministry of Health of Russian Federation, Moscow, Russia.
[Ti] Título:[RAGWEED ALLERGY IN THE SOUTH OF RUSSIA - IN THE CHECHEN REPUBLIC].
[So] Source:Georgian Med News;(266):93-99, 2017 May.
[Is] ISSN:1512-0112
[Cp] País de publicação:Georgia (Republic)
[La] Idioma:rus
[Ab] Resumo:Allergy to ragweed pollen and other weeds is a global problem due to the rapid spread of these grasses around the world. In addition, pollen of short ragweed (Ambrosia, Amb) and mugwort (Artemisia, Art) - one of the main causes of respiratory allergy - seasonal allergic rhinoconjunctivitis (hay fever) with/without bronchial asthma patients living in the South of Russia. Epidemiological studies on the prevalence of Allergy to Amb and Art among patients living in Chechen Republic, absent. Aim - of this retrospective study was to investigate the prevalence of sensitization to weed pollen in patients of Chechnya. We surveyed аllergy (skin prick tests with 13 inhalant allergens) from 845 patients aged 4-68 years, in Urus-Martan for the period 2013-2016 yrs. Polisensitization was defined as the presence of positive skin tests to 2 or more extracts of different groups of allergens. ~26% and 21% of patients in the Chechen Republic have an allergy to Amb and Art, respectively. Further studies at the molecular level will help to establish the geographical variation of the sensitization profile to the major component of Amb and Art, which could have clinical significance in the proper selection of specific immunotherapy.
[Mh] Termos MeSH primário: Ambrosia/imunologia
Hipersensibilidade/epidemiologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Criança
Pré-Escolar
Feminino
Seres Humanos
Hipersensibilidade/imunologia
Masculino
Meia-Idade
Estudos Retrospectivos
Federação Russa/epidemiologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170620
[St] Status:MEDLINE


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[PMID]:28489870
[Au] Autor:Meyer L; Causse R; Pernin F; Scalone R; Bailly G; Chauvel B; Délye C; Le Corre V
[Ad] Endereço:Agroécologie, AgroSup Dijon, INRA, Univ. Bourgogne Franche-Comté, Dijon, France.
[Ti] Título:New gSSR and EST-SSR markers reveal high genetic diversity in the invasive plant Ambrosia artemisiifolia L. and can be transferred to other invasive Ambrosia species.
[So] Source:PLoS One;12(5):e0176197, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ambrosia artemisiifolia L., (common ragweed), is an annual invasive and highly troublesome plant species originating from North America that has become widespread across Europe. New sets of genomic and expressed sequence tag (EST) based simple sequence repeats (SSRs) markers were developed in this species using three approaches. After validation, 13 genomic SSRs and 13 EST-SSRs were retained and used to characterize the genetic diversity and population genetic structure of Ambrosia artemisiifolia populations from the native (North America) and invasive (Europe) ranges of the species. Analysing the mating system based on maternal families did not reveal any departure from complete allogamy and excess homozygosity was mostly due the presence of null alleles. High genetic diversity and patterns of genetic structure in Europe suggest two main introduction events followed by secondary colonization events. Cross-species transferability of the newly developed markers to other invasive species of the Ambrosia genus was assessed. Sixty-five percent and 75% of markers, respectively, were transferable from A. artemisiifolia to Ambrosia psilostachya and Ambrosia tenuifolia. 40% were transferable to Ambrosia trifida, this latter species being seemingly more phylogenetically distantly related to A. artemisiifolia than the former two.
[Mh] Termos MeSH primário: Ambrosia/genética
Etiquetas de Sequências Expressas
Marcadores Genéticos
Variação Genética
Espécies Introduzidas
[Mh] Termos MeSH secundário: Europa (Continente)
América do Norte
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Genetic Markers)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170511
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0176197


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[PMID]:28472131
[Au] Autor:Kiss T; Szabó A; Oszlánczi G; Lukács A; Tímár Z; Tiszlavicz L; Csupor D
[Ad] Endereço:University of Szeged, Faculty of Pharmacy, Department of Pharmacognosy, Szeged, Hungary.
[Ti] Título:Repeated-dose toxicity of common ragweed on rats.
[So] Source:PLoS One;12(5):e0176818, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ambrosia artemisiifolia L. is an invasive species with highly allergenic pollens. Ragweed originates from North America, but it also occurs and is spreading in Europe, causing seasonal allergic rhinitis for millions of people. Recently, the herb of A. artemisiifolia has gained popularity as medicinal plant and food. The effects of its long-term intake are unknown; there are no toxicological data to support the safe use of this plant. The aim of our study was to assess the repeated dose toxicity of A. artemisiifolia on animals. Ragweed puree was administered in low dose (500 mg/kg b. w.) and high dose (1000 mg/kg b. w.) to male Wistar rats according to 407 OECD Guidelines for the Testing of Chemicals. Clinical symptoms, various blood chemical parameters, body weight and organ weights of the rats were measured. Reduced liver function enzymes (AST, ALT), reduced triglyceride level in the low dose and increased carbamide level in the high dose group were observed. The weight of the liver relative to body weight was significantly reduced in both groups, while the brain weight relative to body weight was significantly elevated in both groups. According to our results, the repeated use of ragweed resulted in toxic effects in rats and these results question the safety of long-term human consumption of common ragweed.
[Mh] Termos MeSH primário: Alérgenos/imunologia
Ambrosia
Pólen/imunologia
[Mh] Termos MeSH secundário: Animais
Relação Dose-Resposta Imunológica
Masculino
Ratos
Ratos Wistar
Rinite Alérgica Sazonal/etiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Allergens)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0176818


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[PMID]:28427461
[Au] Autor:Mohieldin EAM; Muddathir AM; Mitsunaga T
[Ad] Endereço:Faculty of Pharmacy, University of Science and Technology, Omdurman, Sudan.
[Ti] Título:Inhibitory activities of selected Sudanese medicinal plants on Porphyromonas gingivalis and matrix metalloproteinase-9 and isolation of bioactive compounds from Combretum hartmannianum (Schweinf) bark.
[So] Source:BMC Complement Altern Med;17(1):224, 2017 Apr 20.
[Is] ISSN:1472-6882
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Periodontal diseases are one of the major health problems and among the most important preventable global infectious diseases. Porphyromonas gingivalis is an anaerobic Gram-negative bacterium which has been strongly implicated in the etiology of periodontitis. Additionally, matrix metalloproteinases-9 (MMP-9) is an important factor contributing to periodontal tissue destruction by a variety of mechanisms. The purpose of this study was to evaluate the selected Sudanese medicinal plants against P. gingivalis bacteria and their inhibitory activities on MMP-9. METHODS: Sixty two methanolic and 50% ethanolic extracts from 24 plants species were tested for antibacterial activity against P. gingivalis using microplate dilution assay method to determine the minimum inhibitory concentration (MIC). The inhibitory activity of seven methanol extracts selected from the 62 extracts against MMP-9 was determined by Colorimetric Drug Discovery Kit. In search of bioactive lead compounds, Combretum hartmannianum bark which was found to be within the most active plant extracts was subjected to various chromatographic (medium pressure liquid chromatography, column chromatography on a Sephadex LH-20, preparative high performance liquid chromatography) and spectroscopic methods (liquid chromatography-mass spectrometry, Nuclear Magnetic Resonance (NMR)) to isolate and characterize flavogalonic acid dilactone and terchebulin as bioactive compounds. RESULTS: About 80% of the crude extracts provided a MIC value ≤4 mg/ml against bacteria. The extracts which revealed the highest potency were: methanolic extracts of Terminalia laxiflora (wood; MIC = 0.25 mg/ml) followed by Acacia totrtilis (bark), Ambrosia maritima (aerial part), Argemone mexicana (seed), C. hartmannianum (bark), Terminalia brownii (wood) and 50% ethanolic extract of T. brownii (bark) with MIC values of 0.5 mg/ml. T. laxiflora (wood) and C. hartmannianum (bark) which belong to combretaceae family showed an inhibitory activity over 50% at the concentration of 10 µg/ml against MMP-9. Additionally, MMP-9 was significantly inhibited by terchebulin with IC value of 6.7 µM. CONCLUSIONS: To the best of our knowledge, flavogalonic acid dilactone and terchebulin were isolated from C. hartmannianium bark for the first time in this study. Because of terchebulin and some crude extracts acting on P. gingivalis bacteria and MMP-9 enzyme that would make them promising natural preference for preventing and treating periodontal diseases.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Combretum/química
Metaloproteinase 9 da Matriz/metabolismo
Doenças Periodontais
Extratos Vegetais/farmacologia
Plantas Medicinais
Porphyromonas gingivalis/efeitos dos fármacos
[Mh] Termos MeSH secundário: Acacia
Ambrosia
Argemone
Taninos Hidrolisáveis/isolamento & purificação
Taninos Hidrolisáveis/farmacologia
Lactonas/isolamento & purificação
Lactonas/farmacologia
Medicina Tradicional Africana
Doenças Periodontais/tratamento farmacológico
Doenças Periodontais/microbiologia
Casca de Planta/química
Extratos Vegetais/química
Sudão
Terminalia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Hydrolyzable Tannins); 0 (Lactones); 0 (Plant Extracts); 0 (terchebulin); EC 3.4.24.35 (Matrix Metalloproteinase 9)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170731
[Lr] Data última revisão:
170731
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170422
[St] Status:MEDLINE
[do] DOI:10.1186/s12906-017-1735-y


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[PMID]:28326906
[Au] Autor:Bernstein DI; Bardelas JA; Svanholm Fogh B; Kaur A; Li Z; Nolte H
[Ad] Endereço:a Bernstein Clinical Research Center and Department of Medicine and Environmental Health , University of Cincinnati , Cincinnati , OH , USA.
[Ti] Título:A practical guide to the sublingual immunotherapy tablet adverse event profile: implications for clinical practice.
[So] Source:Postgrad Med;129(6):590-597, 2017 Aug.
[Is] ISSN:1941-9260
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: Treatment with allergy immunotherapy improves allergic rhinoconjunctivitis, but can also improve comorbidities associated with allergic rhinitis such as asthma. Sublingual immunotherapy (SLIT)-tablets are a convenient and efficacious method of allergy immunotherapy. They are self-administered after the first tablet has been provided under medical supervision. Therapy may elicit local reactions or, rarely, systemic allergic reactions. The objective of this report is to inform healthcare practitioners about the safety and tolerability profile of SLIT-tablets and use this information to provide practical guidance that may inform patients regarding potential adverse reactions and how to manage them. METHODS: Pooled analyses of safety data from completed randomized, multicenter, double-blind, placebo-controlled phase 2 and phase 3 US and EU trials of timothy grass, short ragweed, and SQ house dust mite SLIT-tablets were conducted to characterize safety and tolerability. RESULTS: SLIT-tablets are generally well tolerated. No life-threatening events, serious systemic allergic reactions, or events that compromised the airway have been reported. The most common treatment-related adverse events (AEs) are oral site reactions, most of which begin on day 1 of treatment, recur for less than 2 weeks, and resolve after approximately 30-60 minutes. Systemic allergic reactions have been managed with conventional pharmacotherapy. Reactions treated with epinephrine are uncommon, but have been reported. Treatment of AEs, treatment discontinuation considerations, and patient FAQs regarding SLIT-tablet safety/tolerability are discussed. CONCLUSIONS: This report gives healthcare providers valuable information to educate patients regarding what to expect in terms of SLIT-tablet safety and tolerability. Practical guidance is also provided to ensure proper treatment of any adverse reactions.
[Mh] Termos MeSH primário: Rinite Alérgica/tratamento farmacológico
Rinite Alérgica/imunologia
Imunoterapia Sublingual/efeitos adversos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Ambrosia
Animais
Criança
Pré-Escolar
Método Duplo-Cego
Feminino
Seres Humanos
Masculino
Poaceae
Pyroglyphidae
Autocuidado
Comprimidos
Resultado do Tratamento
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Tablets)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170807
[Lr] Data última revisão:
170807
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170323
[St] Status:MEDLINE
[do] DOI:10.1080/00325481.2017.1302306


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[PMID]:28315734
[Au] Autor:Barton JS; Schomacker R
[Ad] Endereço:Department of Chemistry, Washburn University, 1700 S College Avenue, Topeka, KS 66621, United States. Electronic address: janicebarton@comcast.net.
[Ti] Título:Comparative protein profiles of the Ambrosia plants.
[So] Source:Biochim Biophys Acta;1865(6):633-639, 2017 06.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Ragweed pollen is primarily responsible for the hay fever allergies of sufferers throughout the world. A proteome study of three ragweed plants (Ambrosia artemisiifolia, Ambrosia trifida, and Ambrosia psilostachya) was undertaken to document and compare their protein profiles. Proteins extracted from the pollen of the three plants were subjected to one dimensional electrophoresis followed by tandem liquid chromatography-mass spectroscopy. Peptide sequence mapping permitted discovery of proteins not previously reported for all three plants and 45% of the identified proteins were shared by all three of them. Application of stringent criteria revealed not only a majority of known allergens for short ragweed but also allergens not previously reported for the other two plants. Additionally, potentially allergy inducing enolases are reported for the three plants. These results suggest that all three ragweed plants could contribute to the allergy malady.
[Mh] Termos MeSH primário: Ambrosia/química
Proteínas de Plantas/análise
[Mh] Termos MeSH secundário: Cromatografia Líquida
Proteínas de Plantas/fisiologia
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Plant Proteins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170320
[St] Status:MEDLINE


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[PMID]:28284545
[Au] Autor:Zhao F; Durner J; Winkler JB; Traidl-Hoffmann C; Strom TM; Ernst D; Frank U
[Ad] Endereço:Institute of Biochemical Plant Pathology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany. Electronic address: feng.zhao@helmholtz-muenchen.de.
[Ti] Título:Pollen of common ragweed (Ambrosia artemisiifolia L.): Illumina-based de novo sequencing and differential transcript expression upon elevated NO /O .
[So] Source:Environ Pollut;224:503-514, 2017 May.
[Is] ISSN:1873-6424
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Common ragweed (Ambrosia artemisiifolia L.) is a highly allergenic annual ruderal plant and native to Northern America, but now also spreading across Europe. Air pollution and climate change will not only affect plant growth, pollen production and duration of the whole pollen season, but also the amount of allergenic encoding transcripts and proteins of the pollen. The objective of this study was to get a better understanding of transcriptional changes in ragweed pollen upon NO and O fumigation. This will also contribute to a systems biology approach to understand the reaction of the allergenic pollen to air pollution and climate change. Ragweed plants were grown in climate chambers under controlled conditions and fumigated with enhanced levels of NO and O . Illumina sequencing and de novo assembly revealed significant differentially expressed transcripts, belonging to different gene ontology (GO) terms that were grouped into biological process and molecular function. Transcript levels of the known Amb a ragweed encoding allergens were clearly up-regulated under elevated NO , whereas the amount of allergen encoding transcripts was more variable under elevated O conditions. Moreover transcripts encoding allergen known from other plants could be identified. The transcriptional changes in ragweed pollen upon elevated NO fumigation indicates that air pollution will alter the transcriptome of the pollen. The changed levels of allergenic encoding transcripts may have an influence on the total allergenic potential of ragweed pollen.
[Mh] Termos MeSH primário: Poluentes Atmosféricos/análise
Alérgenos/análise
Ambrosia/crescimento & desenvolvimento
Antígenos de Plantas/genética
Dióxido de Nitrogênio/farmacologia
Ozônio/farmacologia
Extratos Vegetais/genética
Transcriptoma/efeitos dos fármacos
[Mh] Termos MeSH secundário: Ambrosia/efeitos dos fármacos
Ambrosia/genética
Antígenos de Plantas/análise
Mudança Climática
Fumigação
Ontologia Genética
Seres Humanos
América do Norte
Extratos Vegetais/análise
Estações do Ano
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Air Pollutants); 0 (Allergens); 0 (Antigens, Plant); 0 (Plant Extracts); 0 (ragweed pollen); 66H7ZZK23N (Ozone); S7G510RUBH (Nitrogen Dioxide)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170524
[Lr] Data última revisão:
170524
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170313
[St] Status:MEDLINE


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[PMID]:28081194
[Au] Autor:Sancho AI; Wallner M; Hauser M; Nagl B; Himly M; Asam C; Ebner C; Jahn-Schmid B; Bohle B; Ferreira F
[Ad] Endereço:Christian Doppler Laboratory for Allergy Diagnosis and Therapy, Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
[Ti] Título:T Cell Epitope-Containing Domains of Ragweed Amb a 1 and Mugwort Art v 6 Modulate Immunologic Responses in Humans and Mice.
[So] Source:PLoS One;12(1):e0169784, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Ragweed (Ambrosia artemisiifolia) and mugwort (Artemisia vulgaris) are the major cause of pollen allergy in late summer. Allergen-specific lymphocytes are crucial for immune modulation during immunotherapy. We sought to generate and pre-clinically characterise highly immunogenic domains of the homologous pectate lyases in ragweed (Amb a 1) and mugwort pollen (Art v 6) for immunotherapy. METHODS: Domains of Amb a 1 (Amb a 1α) and Art v 6 (Art v 6α) and a hybrid molecule, consisting of both domains, were designed, expressed in E. coli and purified. Human IgE reactivity and allergenicity were assessed by ELISA and mediator release experiments using ragweed and mugwort allergic patients. Moreover, T cell proliferation was determined. Blocking IgG antibodies and cytokine production in BALB/c mice were studied by ELISA and ELISPOT. RESULTS: The IgE binding capacity and in vitro allergenic activity of the Amb a 1 and Art v 6 domains and the hybrid were either greatly reduced or abolished. The recombinant proteins induced T cell proliferative responses comparable to those of the natural allergens, indicative of retained allergen-specific T cell response. Mice immunisation with the hypoallergens induced IL-4, IL-5, IL-13 and IFN-γ production after antigen-specific in vitro re-stimulation of splenocytes. Moreover, murine IgG antibodies that inhibited specific IgE binding of ragweed and mugwort pollen allergic patients were detected. CONCLUSION: Accumulation of T cell epitopes and deletion of IgE reactive areas of Amb a 1 and Art v 6, modulated the immunologic properties of the allergen immuno-domains, leading to promising novel candidates for therapeutic approach.
[Mh] Termos MeSH primário: Ambrosia/imunologia
Antígenos de Plantas/metabolismo
Artemisia/imunologia
Epitopos de Linfócito T/imunologia
Proteínas de Plantas/metabolismo
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Alérgenos/imunologia
Ambrosia/química
Sequência de Aminoácidos
Animais
Antígenos de Plantas/genética
Antígenos de Plantas/isolamento & purificação
Artemisia/química
Criança
Dicroísmo Circular
Escherichia coli/metabolismo
Feminino
Seres Humanos
Imunoglobulina E/imunologia
Imunoglobulina E/metabolismo
Imunoglobulina G/imunologia
Imunoglobulina G/metabolismo
Interferon gama/análise
Interleucinas/análise
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Meia-Idade
Proteínas de Plantas/genética
Proteínas de Plantas/isolamento & purificação
Ratos
Proteínas Recombinantes/biossíntese
Proteínas Recombinantes/imunologia
Proteínas Recombinantes/isolamento & purificação
Linfócitos T/citologia
Linfócitos T/imunologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Allergens); 0 (Amb a I protein, Ambrosia artemisiifolia); 0 (Antigens, Plant); 0 (Epitopes, T-Lymphocyte); 0 (Immunoglobulin G); 0 (Interleukins); 0 (Plant Proteins); 0 (Recombinant Proteins); 37341-29-0 (Immunoglobulin E); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170824
[Lr] Data última revisão:
170824
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170113
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0169784


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Texto completo
[PMID]:27838323
[Au] Autor:Nolte H; Casale TB; Lockey RF; Fogh BS; Kaur A; Lu S; Nelson HS
[Ad] Endereço:Research and Development, Merck & Co., Inc., Kenilworth, NJ. Electronic address: hendrik.nolte@merck.com.
[Ti] Título:Epinephrine Use in Clinical Trials of Sublingual Immunotherapy Tablets.
[So] Source:J Allergy Clin Immunol Pract;5(1):84-89.e3, 2017 Jan - Feb.
[Is] ISSN:2213-2201
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Allergy immunotherapy can result in systemic allergic reactions and even life-threatening anaphylaxis requiring epinephrine administration. OBJECTIVE: The objective of this study was to describe epinephrine use in the clinical trial development programs of 3 rapidly dissolving sublingual immunotherapy tablets (SLIT-tablets; Merck & Co., Inc., Kenilworth, NJ/ALK, Hørsholm, Denmark/Torii Pharmaceutical Co., Ltd., Tokyo, Japan). METHODS: Data on epinephrine use were collected from 13 timothy grass SLIT-tablet trials (MK-7243; ≤2800 bioequivalent allergen units/75,000 SQ-T dose, n = 2497; placebo, n = 2139), 5 short ragweed SLIT-tablet trials (MK-3641; ≤12 Amb a 1-U, n = 1725; placebo, n = 770), and 11 house dust mite (HDM) SLIT-tablet trials (MK-8237; ≤12 SQ-HDM; n = 3930; placebo, n = 2246). RESULTS: In grass SLIT-tablet trials, epinephrine was used 13 times (grass SLIT-tablet, n = 10; placebo, n = 3). Eight administrations were for grass SLIT-tablet-related adverse events (AEs): 4 for systemic allergic reactions and 4 for local mouth and/or throat swelling. In ragweed SLIT-tablet trials, epinephrine was used 9 times in 8 subjects (ragweed SLIT-tablet, n = 7; placebo, n = 1 [2 administrations for protracted anaphylaxis]). Four administrations were for ragweed SLIT-tablet-related AEs: 1 for systemic allergic reaction and 3 for local mouth and/or pharynx/throat swelling. In HDM SLIT-tablet trials, epinephrine was administered 13 times (HDM SLIT-tablet, n = 8; placebo, n = 5). Four administrations were for HDM SLIT-tablet-related AEs: 1 for systemic allergic reaction and 3 for local events. Of the 16 epinephrine administrations for events related to SLIT-tablet treatment, 11 occurred within the first week of treatment (7 administrations on day 1) and 5 were subject self-administered. CONCLUSIONS: Epinephrine administrations in response to SLIT-tablet-related reactions in clinical trials are uncommon, typically occur within the first week of treatment, and are rarely self-administered. All SLIT-tablet-related events treated with epinephrine were nonserious.
[Mh] Termos MeSH primário: Anafilaxia/prevenção & controle
Antígenos de Dermatophagoides/uso terapêutico
Antígenos de Plantas/uso terapêutico
Asma/terapia
Epinefrina/administração & dosagem
Rinite Alérgica/terapia
Imunoterapia Sublingual/métodos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Ambrosia
Anafilaxia/etiologia
Animais
Asma/complicações
Asma/imunologia
Criança
Pré-Escolar
Feminino
Seres Humanos
Masculino
Meia-Idade
Phleum
Pyroglyphidae
Rinite Alérgica/complicações
Rinite Alérgica/imunologia
Imunoterapia Sublingual/efeitos adversos
Comprimidos
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; CLINICAL TRIAL, PHASE II; CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Antigens, Dermatophagoides); 0 (Antigens, Plant); 0 (Tablets); YKH834O4BH (Epinephrine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161114
[St] Status:MEDLINE



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