Base de dados : MEDLINE
Pesquisa : D02.241.081.114.875 [Categoria DeCS]
Referências encontradas : 469 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 47 ir para página                         

  1 / 469 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29317660
[Au] Autor:Fellows R; Denizot J; Stellato C; Cuomo A; Jain P; Stoyanova E; Balázsi S; Hajnády Z; Liebert A; Kazakevych J; Blackburn H; Corrêa RO; Fachi JL; Sato FT; Ribeiro WR; Ferreira CM; Perée H; Spagnuolo M; Mattiuz R; Matolcsi C; Guedes J; Clark J; Veldhoen M; Bonaldi T; Vinolo MAR; Varga-Weisz P
[Ad] Endereço:Nuclear Dynamics, Babraham Institute, Cambridge, CB22 3AT, UK.
[Ti] Título:Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases.
[So] Source:Nat Commun;9(1):105, 2018 01 09.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The recently discovered histone post-translational modification crotonylation connects cellular metabolism to gene regulation. Its regulation and tissue-specific functions are poorly understood. We characterize histone crotonylation in intestinal epithelia and find that histone H3 crotonylation at lysine 18 is a surprisingly abundant modification in the small intestine crypt and colon, and is linked to gene regulation. We show that this modification is highly dynamic and regulated during the cell cycle. We identify class I histone deacetylases, HDAC1, HDAC2, and HDAC3, as major executors of histone decrotonylation. We show that known HDAC inhibitors, including the gut microbiota-derived butyrate, affect histone decrotonylation. Consistent with this, we find that depletion of the gut microbiota leads to a global change in histone crotonylation in the colon. Our results suggest that histone crotonylation connects chromatin to the gut microbiota, at least in part, via short-chain fatty acids and HDACs.
[Mh] Termos MeSH primário: Crotonatos/metabolismo
Ácidos Graxos Voláteis/fisiologia
Histona Desacetilases/metabolismo
Histonas/metabolismo
Mucosa Intestinal/metabolismo
[Mh] Termos MeSH secundário: Acilação
Animais
Ciclo Celular
Colo/metabolismo
Colo/microbiologia
Microbioma Gastrointestinal
Células HCT116
Inibidores de Histona Desacetilases
Seres Humanos
Masculino
Camundongos Endogâmicos C57BL
Processamento de Proteína Pós-Traducional
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Crotonates); 0 (Fatty Acids, Volatile); 0 (Histone Deacetylase Inhibitors); 0 (Histones); EC 3.5.1.98 (Histone Deacetylases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02651-5


  2 / 469 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28461106
[Au] Autor:Staun-Ram E; Miller A
[Ad] Endereço:Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
[Ti] Título:Effector and regulatory B cells in Multiple Sclerosis.
[So] Source:Clin Immunol;184:11-25, 2017 11.
[Is] ISSN:1521-7035
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The role of B cells in the pathogenesis of Multiple Sclerosis (MS), an autoimmune neurodegenerative disease, is becoming eminent in recent years, but the specific contribution of the distinct B cell subsets remains to be elucidated. Several B cell subsets have shown regulatory, anti-inflammatory capacities in response to stimuli in vitro, as well as in the animal model of MS: Experimental Autoimmune Encephalomyelitis (EAE). However, the functional role of the B regulatory cells (Bregs) in vivo and specifically in the human disease is yet to be clarified. In the present review, we have summarized the updated information on the roles of effector and regulatory B cells in MS and the immune-modulatory effects of MS therapeutic agents on their phenotype and function.
[Mh] Termos MeSH primário: Subpopulações de Linfócitos B/imunologia
Linfócitos B Reguladores/imunologia
Encefalomielite Autoimune Experimental/imunologia
Esclerose Múltipla/imunologia
[Mh] Termos MeSH secundário: Alemtuzumab/uso terapêutico
Animais
Crotonatos/uso terapêutico
Fumarato de Dimetilo/uso terapêutico
Cloridrato de Fingolimode/uso terapêutico
Acetato de Glatiramer/uso terapêutico
Seres Humanos
Fatores Imunológicos/uso terapêutico
Imunossupressores/uso terapêutico
Interferon beta/uso terapêutico
Esclerose Múltipla/tratamento farmacológico
Natalizumab/uso terapêutico
Rituximab/uso terapêutico
Toluidinas/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Crotonates); 0 (Immunologic Factors); 0 (Immunosuppressive Agents); 0 (Natalizumab); 0 (Toluidines); 1C058IKG3B (teriflunomide); 3A189DH42V (Alemtuzumab); 4F4X42SYQ6 (Rituximab); 5M691HL4BO (Glatiramer Acetate); 77238-31-4 (Interferon-beta); FO2303MNI2 (Dimethyl Fumarate); G926EC510T (Fingolimod Hydrochloride)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180206
[Lr] Data última revisão:
180206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  3 / 469 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29050931
[Au] Autor:Jiang L; Zhang W; Li W; Ling C; Jiang M
[Ad] Endereço:Department of Respiratory Diseases, The First Affiliated Hospital of Soochow University, 215006, China.
[Ti] Título:Anti-inflammatory drug, leflunomide and its metabolite teriflunomide inhibit NSCLC proliferation in vivo and in vitro.
[So] Source:Toxicol Lett;282:154-165, 2018 Jan 05.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Lung cancer causes more than 150000 deaths annually in the United States alone, of which non-small cell lung cancer (NSCLC) accounts for 80%. Our studies demonstrated that NSCLC cells were sensitive to leflunomide and its metabolite teriflunomide, a FDA approved drug, which was a well-known immunomodulatory drug for relapsing multiple sclerosis (MS). In the present studies, we found first time that they displayed anti-tumor activity of NSCLC in vitro and in vivo. Potent anti-cancer effects in NSCLC in vitro, including inhibiting NSCLC cells viability, arresting cell cycle at the G0/G1 phase, inducing cell apoptosis, delaying and suppressing NSCLC cells colony-forming ability and cell motility, could be achieved with this agent. Meanwhile, we provided evidence that these effects were applicable in vivo by using H460 cells xenograft model in nude mice. In addition, to comprehensively clarify the mechanisms of teriflunomide in NSCLC, we explored a genome-wide transcriptomic analysis, and found that teriflunomide was involved in multiple signaling pathways and cellular processes, such as cell cycle, apoptosis, MAPK and p53 signaling pathway. Taken together, the results of our studies provided insights into a novel anti-cancer effect of leflunomide and teriflunomide on NSCLC and might open new therapeutic avenues for the treatment of NSCLC.
[Mh] Termos MeSH primário: Anti-Inflamatórios/farmacologia
Antineoplásicos/farmacologia
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico
Proliferação Celular/efeitos dos fármacos
Crotonatos/farmacologia
Isoxazóis/farmacologia
Toluidinas/farmacologia
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Carcinoma Pulmonar de Células não Pequenas/patologia
Linhagem Celular Tumoral
Movimento Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Feminino
Seres Humanos
Camundongos Nus
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents); 0 (Antineoplastic Agents); 0 (Crotonates); 0 (Isoxazoles); 0 (Toluidines); 1C058IKG3B (teriflunomide); G162GK9U4W (leflunomide)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171201
[Lr] Data última revisão:
171201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171021
[St] Status:MEDLINE


  4 / 469 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28838689
[Au] Autor:Forrester SG; Foster J; Robert S; Salim L; Desaulniers JP
[Ad] Endereço:Faculty of Science, University of Ontario Institute of Technology, Oshawa, ON L1H 7K4, Canada.
[Ti] Título:Efficient synthesis of the GABA receptor agonist trans-4-aminocrotonic acid (TACA).
[So] Source:Bioorg Med Chem Lett;27(18):4512-4513, 2017 09 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Investigations into the pharmacology of different types of cys-loop GABA receptor have relied for years on the chemical modification of GABA-like compounds. The GABA metabolite GABOB is an attractive molecule to modify due to its convenient chemical structure. In the process of developing new GABA-mimic compounds from GABOB as a starting compound three small molecule GABA derivatives were synthesized using a variety of chemical transformations. Amongst these, a new and reliable method to synthesize TACA (trans-4-aminocrotonic acid) is reported.
[Mh] Termos MeSH primário: Crotonatos/farmacologia
Agonistas de Receptores de GABA-A/farmacologia
Receptores de GABA-A/metabolismo
[Mh] Termos MeSH secundário: Animais
Crotonatos/síntese química
Crotonatos/química
Relação Dose-Resposta a Droga
Agonistas de Receptores de GABA-A/síntese química
Agonistas de Receptores de GABA-A/química
Estrutura Molecular
Oócitos/efeitos dos fármacos
Relação Estrutura-Atividade
Xenopus laevis
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Crotonates); 0 (GABA-A Receptor Agonists); 0 (Receptors, GABA-A); 25747-40-4 (4-aminocrotonic acid)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171125
[Lr] Data última revisão:
171125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170826
[St] Status:MEDLINE


  5 / 469 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28796815
[Au] Autor:Modica CM; Schweser F; Sudyn ML; Bertolino N; Preda M; Polak P; Siebert DM; Krawiecki JC; Sveinsson M; Hagemeier J; Dwyer MG; Pol S; Zivadinov R
[Ad] Endereço:Neuroscience Program, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York, United States of America.
[Ti] Título:Effect of teriflunomide on cortex-basal ganglia-thalamus (CxBGTh) circuit glutamatergic dysregulation in the Theiler's Murine Encephalomyelitis Virus mouse model of multiple sclerosis.
[So] Source:PLoS One;12(8):e0182729, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Pathology of gray matter is associated with development of physical and cognitive disability in patients with multiple sclerosis. In particular, glutamatergic dysregulation in the cortex-basal ganglia-thalamus (CxBGTh) circuit could be associated with decline in these behaviors. OBJECTIVES: To investigate the effect of an immunomodulatory therapy (teriflunomide, Aubagio®) on changes of the CxBGTh loop in the Theiler's Murine Encephalomyelitis Virus, (TMEV) mouse model of MS. METHODS: Forty-eight (48) mice were infected with TMEV, treated with teriflunomide (24) or control vehicle (24) and followed for 39 weeks. Mice were examined with MRS and volumetric MRI scans (0, 8, 26, and 39 weeks) in the cortex, basal ganglia and thalamus, using a 9.4T scanner, and with behavioral tests (0, 4, 8, 12, 17, 26, and 39 weeks). Within conditions, MRI measures were compared between two time points by paired samples t-test and across multiple time points by repeated measures ANOVA (rmANOVA), and between conditions by independent samples t-test and rmANOVA, respectively. Data were considered as significant at the p<0.01 level and as a trend at p<0.05 level. RESULTS: In the thalamus, the teriflunomide arm exhibited trends toward decreased glutamate levels at 8 and 26 weeks compared to the control arm (p = 0.039 and p = 0.026), while the control arm exhibited a trend toward increased glutamate between 0 to 8 weeks (p = 0.045). In the basal ganglia, the teriflunomide arm exhibited a trend toward decreased glutamate earlier than the control arm, from 0 to 8 weeks (p = 0.011), resulting in decreased glutamate compared to the control arm at 8 weeks (p = 0.016). CONCLUSIONS: Teriflunomide may reduce possible excitotoxicity in the thalamus and basal ganglia by lowering glutamate levels.
[Mh] Termos MeSH primário: Gânglios da Base/efeitos dos fármacos
Crotonatos/farmacologia
Esclerose Múltipla/tratamento farmacológico
Tálamo/efeitos dos fármacos
Toluidinas/farmacologia
[Mh] Termos MeSH secundário: Animais
Gânglios da Base/metabolismo
Linhagem Celular
Corpo Caloso/efeitos dos fármacos
Corpo Caloso/metabolismo
Modelos Animais de Doenças
Avaliação Pré-Clínica de Medicamentos
Fármacos atuantes sobre Aminoácidos Excitatórios/farmacologia
Feminino
Ácido Glutâmico/metabolismo
Mesocricetus
Camundongos
Mielite/tratamento farmacológico
Tálamo/metabolismo
Ácido gama-Aminobutírico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Crotonates); 0 (Excitatory Amino Acid Agents); 0 (Toluidines); 1C058IKG3B (teriflunomide); 3KX376GY7L (Glutamic Acid); 56-12-2 (gamma-Aminobutyric Acid)
[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:170811
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182729


  6 / 469 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28499873
[Au] Autor:Teranishi K
[Ad] Endereço:Graduate School of Bioresources, Mie University, 1577 Kurimamachiya, Tsu, Mie 514-8507, Japan. Electronic address: teranisi@bio.mie-u.ac.jp.
[Ti] Título:Inhibition of bioluminescence in the living gills of the luminous fungus Mycena chlorophos by trans-4-aminocinnamic acid.
[So] Source:Biochem Biophys Res Commun;488(2):335-339, 2017 Jun 24.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The living gills of the fungus Mycena chlorophos spontaneously emit green light. It was previously reported that trans-4-hydroxycinnamic acid and trans-3,4-dihydroxycinnnamic acid are essential for the bright light production in the living gills. However, the chemical mechanisms underlying their bioluminescence are unknown. In the present study, trans-4-aminocinnamic acid was found to inhibit light production in the living gills. The concentrations of trans-4-aminocinnamic acid that inhibited the bioluminescence intensity by 50% of initial values for immature and mature gills were 0.07 µM and 4 µM, respectively. Approximately 20% of the bioluminescence intensity of the immature and mature gills was not inhibited by a further increase in the concentration of trans-4-aminocinnamic acid. Moreover, the bioluminescence that was activated by trans-4-hydroxycinnamic acid or trans-3,4-dihydroxycinnamic acid (0.01 mM) was completely inhibited by trans-4-aminocinnamic acid. Therefore, trans-4-hydroxycinnamic acid and trans-3,4-dihydroxycinnamic acid functioned for the bioluminescence that was inhibited by trans-4-aminocinnamic acid. trans-4-Aminocinnamic acid strongly bound to the bioluminescence system(s) and withstood rinsing of the gills with 10 mM phosphate buffer (pH = 7), and high concentrations of trans-4-hydroxycinnamic acid (1 mM) and trans-3,4-dihydroxycinnamic acid (0.1 mM) functioned to displace trans-4-aminocinnamic acid from the bioluminescence system(s) and reactivate bioluminescence. Benzenamine, trans-cinnamic acid, trans-2-aminocinnamic acid, and trans-3-aminocinnamic acid did not inhibit bioluminescence. Therefore, the structure-specific inhibition by trans-4-aminocinnamic acid suggested that the 4-hydroxy group in trans-4-hydroxycinnamic acid and trans-3,4-dihydroxycinnamic acid molecules plays a functional role in the bioluminescence reaction.
[Mh] Termos MeSH primário: Basidiomycota/química
Basidiomycota/efeitos dos fármacos
Crotonatos/farmacologia
Carpóforos/química
Carpóforos/efeitos dos fármacos
Luminescência
[Mh] Termos MeSH secundário: Animais
Basidiomycota/metabolismo
Carpóforos/metabolismo
Medições Luminescentes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Crotonates); 25747-40-4 (4-aminocrotonic acid)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170921
[Lr] Data última revisão:
170921
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170514
[St] Status:MEDLINE


  7 / 469 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
Texto completo
[PMID]:28440858
[Au] Autor:Filippini G; Del Giovane C; Clerico M; Beiki O; Mattoscio M; Piazza F; Fredrikson S; Tramacere I; Scalfari A; Salanti G
[Ad] Endereço:Scientific Direction, Fondazione IRCCS, Istituto Neurologico Carlo Besta, via Celoria, 11, Milan, Italy, 20133.
[Ti] Título:Treatment with disease-modifying drugs for people with a first clinical attack suggestive of multiple sclerosis.
[So] Source:Cochrane Database Syst Rev;4:CD012200, 2017 Apr 25.
[Is] ISSN:1469-493X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The treatment of multiple sclerosis has changed over the last 20 years. The advent of disease-modifying drugs in the mid-1990s heralded a period of rapid progress in the understanding and management of multiple sclerosis. With the support of magnetic resonance imaging early diagnosis is possible, enabling treatment initiation at the time of the first clinical attack. As most of the disease-modifying drugs are associated with adverse events, patients and clinicians need to weigh the benefit and safety of the various early treatment options before taking informed decisions. OBJECTIVES: 1. to estimate the benefit and safety of disease-modifying drugs that have been evaluated in all studies (randomised or non-randomised) for the treatment of a first clinical attack suggestive of MS compared either with placebo or no treatment;2. to assess the relative efficacy and safety of disease-modifying drugs according to their benefit and safety;3. to estimate the benefit and safety of disease-modifying drugs that have been evaluated in all studies (randomised or non-randomised) for treatment started after a first attack ('early treatment') compared with treatment started after a second attack or at another later time point ('delayed treatment'). SEARCH METHODS: We searched the Cochrane Multiple Sclerosis and Rare Diseases of the CNS Group Trials Register, MEDLINE, Embase, CINAHL, LILACS, clinicaltrials.gov, the WHO trials registry, and US Food and Drug Administration (FDA) reports, and searched for unpublished studies (until December 2016). SELECTION CRITERIA: We included randomised and observational studies that evaluated one or more drugs as monotherapy in adult participants with a first clinical attack suggestive of MS. We considered evidence on alemtuzumab, azathioprine, cladribine, daclizumab, dimethyl fumarate, fingolimod, glatiramer acetate, immunoglobulins, interferon beta-1b, interferon beta-1a (Rebif®, Avonex®), laquinimod, mitoxantrone, natalizumab, ocrelizumab, pegylated interferon beta-1a, rituximab and teriflunomide. DATA COLLECTION AND ANALYSIS: Two teams of three authors each independently selected studies and extracted data. The primary outcomes were disability-worsening, relapses, occurrence of at least one serious adverse event (AE) and withdrawing from the study or discontinuing the drug because of AEs. Time to conversion to clinically definite MS (CDMS) defined by Poser diagnostic criteria, and probability to discontinue the treatment or dropout for any reason were recorded as secondary outcomes. We synthesized study data using random-effects meta-analyses and performed indirect comparisons between drugs. We calculated odds ratios (OR) and hazard ratios (HR) along with relative 95% confidence intervals (CI) for all outcomes. We estimated the absolute effects only for primary outcomes. We evaluated the credibility of the evidence using the GRADE system. MAIN RESULTS: We included 10 randomised trials, eight open-label extension studies (OLEs) and four cohort studies published between 2010 and 2016. The overall risk of bias was high and the reporting of AEs was scarce. The quality of the evidence associated with the results ranges from low to very low. Early treatment versus placebo during the first 24 months' follow-upThere was a small, non-significant advantage of early treatment compared with placebo in disability-worsening (6.4% fewer (13.9 fewer to 3 more) participants with disability-worsening with interferon beta-1a (Rebif®) or teriflunomide) and in relapses (10% fewer (20.3 fewer to 2.8 more) participants with relapses with teriflunomide). Early treatment was associated with 1.6% fewer participants with at least one serious AE (3 fewer to 0.2 more). Participants on early treatment were on average 4.6% times (0.3 fewer to 15.4 more) more likely to withdraw from the study due to AEs. This result was mostly driven by studies on interferon beta 1-b, glatiramer acetate and cladribine that were associated with significantly more withdrawals for AEs. Early treatment decreased the hazard of conversion to CDMS (HR 0.53, 95% CI 0.47 to 0.60). Comparing active interventions during the first 24 months' follow-upIndirect comparison of interferon beta-1a (Rebif®) with teriflunomide did not show any difference on reducing disability-worsening (OR 0.84, 95% CI 0.43 to 1.66). We found no differences between the included drugs with respect to the hazard of conversion to CDMS. Interferon beta-1a (Rebif®) and teriflunomide were associated with fewer dropouts because of AEs compared with interferon beta-1b, cladribine and glatiramer acetate (ORs range between 0.03 and 0.29, with substantial uncertainty). Early versus delayed treatmentWe did not find evidence of differences between early and delayed treatments for disability-worsening at a maximum of five years' follow-up (3% fewer participants with early treatment (15 fewer to 11.1 more)). There was important variability across interventions; early treatment with interferon beta-1b considerably reduced the odds of participants with disability-worsening during three and five years' follow-up (OR 0.52, 95% CI 0.32 to 0.84 and OR 0.57, 95% CI 0.36 to 0.89). The early treatment group had 19.6% fewer participants with relapses (26.7 fewer to 12.7 fewer) compared to late treatment at a maximum of five years' follow-up and early treatment decreased the hazard of conversion to CDMS at any follow-up up to 10 years (i.e. over five years' follow-up HR 0.62, 95% CI 0.53 to 0.73). We did not draw any conclusions on long-term serious AEs or discontinuation due to AEs because of inadequacies in the available data both in the included OLEs and cohort studies. AUTHORS' CONCLUSIONS: Very low-quality evidence suggests a small and uncertain benefit with early treatment compared with placebo in reducing disability-worsening and relapses. The advantage of early treatment compared with delayed on disability-worsening was heterogeneous depending on the actual drug used and based on very low-quality evidence. Low-quality evidence suggests that the chances of relapse are less with early treatment compared with delayed. Early treatment reduced the hazard of conversion to CDMS compared either with placebo, no treatment or delayed treatment, both in short- and long-term follow-up. Low-quality evidence suggests that early treatment is associated with fewer participants with at least one serious AE compared with placebo. Very low-quality evidence suggests that, compared with placebo, early treatment leads to more withdrawals or treatment discontinuation due to AEs. Difference between drugs on short-term benefit and safety was uncertain because few studies and only indirect comparisons were available. Long-term safety of early treatment is uncertain because of inadequately reported or unavailable data.
[Mh] Termos MeSH primário: Adjuvantes Imunológicos/uso terapêutico
Imunossupressores/uso terapêutico
Esclerose Múltipla/tratamento farmacológico
[Mh] Termos MeSH secundário: Adjuvantes Imunológicos/efeitos adversos
Cladribina/efeitos adversos
Cladribina/uso terapêutico
Estudos de Coortes
Crotonatos/efeitos adversos
Crotonatos/uso terapêutico
Progressão da Doença
Acetato de Glatiramer/efeitos adversos
Acetato de Glatiramer/uso terapêutico
Seres Humanos
Imunossupressores/efeitos adversos
Interferon beta-1a/efeitos adversos
Interferon beta-1a/uso terapêutico
Viés de Publicação
Ensaios Clínicos Controlados Aleatórios como Assunto
Recidiva
Fatores de Tempo
Toluidinas/efeitos adversos
Toluidinas/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (Crotonates); 0 (Immunosuppressive Agents); 0 (Toluidines); 1C058IKG3B (teriflunomide); 47M74X9YT5 (Cladribine); 5M691HL4BO (Glatiramer Acetate); XRO4566Q4R (Interferon beta-1a)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170802
[Lr] Data última revisão:
170802
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170426
[St] Status:MEDLINE
[do] DOI:10.1002/14651858.CD012200.pub2


  8 / 469 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28209373
[Au] Autor:Soini E; Joutseno J; Sumelahti ML
[Ad] Endereço:ESiOR Oy, Kuopio, Finland. Electronic address: erkki.soini@esior.fi.
[Ti] Título:Cost-utility of First-line Disease-modifying Treatments for Relapsing-Remitting Multiple Sclerosis.
[So] Source:Clin Ther;39(3):537-557.e10, 2017 Mar.
[Is] ISSN:1879-114X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: This study evaluated the cost-effectiveness of first-line treatments of relapsing-remitting multiple sclerosis (RRMS) (dimethyl fumarate [DMF] 240 mg PO BID, teriflunomide 14 mg once daily, glatiramer acetate 20 mg SC once daily, interferon [IFN]-ß1a 44 µg TIW, IFN-ß1b 250 µg EOD, and IFN-ß1a 30 µg IM QW) and best supportive care (BSC) in the health care payer setting in Finland. METHODS: The primary outcome was the modeled incremental cost-effectiveness ratio (ICER; €/quality-adjusted life-year [QALY] gained, 3%/y discounting). Markov cohort modeling with a 15-year time horizon was employed. During each 1-year modeling cycle, patients either maintained the Expanded Disability Status Scale (EDSS) score or experienced progression, developed secondary progressive MS (SPMS) or showed EDSS progression in SPMS, experienced relapse with/without hospitalization, experienced an adverse event (AE), or died. Patients׳ characteristics, RRMS progression probabilities, and standardized mortality ratios were derived from a registry of patients with MS in Finland. A mixed-treatment comparison (MTC) informed the treatment effects. Finnish EuroQol Five-Dimensional Questionnaire, Three-Level Version quality-of-life and direct-cost estimates associated with EDSS scores, relapses, and AEs were applied. Four approaches were used to assess the outcomes: cost-effectiveness plane and efficiency frontiers (relative value of efficient treatments); cost-effectiveness acceptability frontier, which demonstrated optimal treatment to maximize net benefit; Bayesian treatment ranking (BTR); and an impact investment assessment (IIA; a cost-benefit assessment), which increased the clinical interpretation and appeal of modeled outcomes in terms of absolute benefit gained with fixed drug-related budget. Robustness of results was tested extensively with sensitivity analyses. FINDINGS: Based on the modeled results, teriflunomide was less costly, with greater QALYs, versus glatiramer acetate and the IFNs. Teriflunomide had the lowest ICER (24,081) versus BSC. DMF brought marginally more QALYs (0.089) than did teriflunomide, with greater costs over the 15 years. The ICER for DMF versus teriflunomide was 75,431. Teriflunomide had >50% cost-effectiveness probabilities with a willingness-to-pay threshold of <€77,416/QALY gained. According to BTR, teriflunomide was first-best among the disease-modifying therapies, with potential willingness-to-pay thresholds of up to €68,000/QALY gained. In the IIA, teriflunomide was associated with the longest incremental quality-adjusted survival and time without cane use. Generally, primary outcomes results were robust, based on the sensitivity analyses. The results were sensitive only to large changes in analysis perspective or mixed-treatment comparison. IMPLICATIONS: The results were sensitive only to large changes in analysis perspective or MTC. Based on the analyses, teriflunomide was cost-effective versus BSC or DMF with the common threshold values, was dominant versus other first-line RRMS treatments, and provided the greatest impact on investment. Teriflunomide is potentially the most cost-effective option among first-line treatments of RRMS in Finland.
[Mh] Termos MeSH primário: Crotonatos/uso terapêutico
Fumarato de Dimetilo/uso terapêutico
Acetato de Glatiramer/uso terapêutico
Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico
Toluidinas/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Teorema de Bayes
Análise Custo-Benefício
Feminino
Seres Humanos
Masculino
Esclerose Múltipla/tratamento farmacológico
Anos de Vida Ajustados por Qualidade de Vida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Crotonates); 0 (Toluidines); 1C058IKG3B (teriflunomide); 5M691HL4BO (Glatiramer Acetate); FO2303MNI2 (Dimethyl Fumarate)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170218
[St] Status:MEDLINE


  9 / 469 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28180112
[Au] Autor:Rumah KR; Vartanian TK; Fischetti VA
[Ad] Endereço:Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University New York, NY, USA.
[Ti] Título:Oral Multiple Sclerosis Drugs Inhibit the Growth of Epsilon Toxin Producing Gut Bacterium, .
[So] Source:Front Cell Infect Microbiol;7:11, 2017.
[Is] ISSN:2235-2988
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:There are currently three oral medications approved for the treatment of multiple sclerosis (MS). Two of these medications, Fingolimod, and Teriflunomide, are considered to be anti-inflammatory agents, while dimethyl fumarate (DMF) is thought to trigger a robust antioxidant response, protecting vulnerable cells during an MS attack. We previously proposed that epsilon toxin from the gut bacterium, , may initiate newly forming MS lesions due to its tropism for blood-brain barrier (BBB) vasculature and central nervous system myelin. Because gut microbiota will be exposed to these oral therapies prior to systemic absorption, we sought to determine if these compounds affect growth . Here we show that Fingolimod, Teriflunomide, and DMF indeed inhibit growth. Furthermore, several compounds similar to DMF in chemical structure, namely α, ß unsaturated carbonyls, also known as Michael acceptors, inhibit . Sphingosine, a Fingolimod homolog with known antibacterial properties, proved to be a potent inhibitor with a Minimal Inhibitory Concentration similar to that of Fingolimod. These findings suggest that currently approved oral MS therapies and structurally related compounds possess antibacterial properties that may alter the gut microbiota. Moreover, inhibition of growth and resulting blockade of epsilon toxin production may contribute to the clinical efficacy of these disease-modifying drugs.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Clostridium perfringens/efeitos dos fármacos
Clostridium perfringens/crescimento & desenvolvimento
Crotonatos/farmacologia
Fumarato de Dimetilo/farmacologia
Cloridrato de Fingolimode/farmacologia
Toluidinas/farmacologia
[Mh] Termos MeSH secundário: Testes de Sensibilidade Microbiana
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Crotonates); 0 (Toluidines); 1C058IKG3B (teriflunomide); FO2303MNI2 (Dimethyl Fumarate); G926EC510T (Fingolimod Hydrochloride)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170210
[St] Status:MEDLINE
[do] DOI:10.3389/fcimb.2017.00011


  10 / 469 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27704206
[Au] Autor:Bua A; Ruggeri M; Zanetti S; Molicotti P
[Ad] Endereço:Department of Biomedical Sciences, Section of Experimental and Clinical Microbiology, University of Sassari, Viale San Pietro 43B, 07100, Sassari, Italy. ale.b76@email.it.
[Ti] Título:Effect of teriflunomide on QuantiFERON-TB Gold results.
[So] Source:Med Microbiol Immunol;206(1):73-75, 2017 Feb.
[Is] ISSN:1432-1831
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Multiple sclerosis is a chronic inflammatory disease of the central nervous system characterized by damage to myelin and axons, over time leading to progressive neuronal degeneration and microglial activation. There is still no curative treatment, but during the last 20 years eight different therapies have become available including interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate, natalizumab, fingolimod, alemtuzumab, mitoxantrone and teriflunomide. Teriflunomide is an immunomodulatory drug that exerts an inhibitory effect on T cell activation in central nervous system of the patients with multiple sclerosis. We determined whether teriflunomide affect the production of interferon-gamma, interleukin-2 and tumor-necrosis-factor-α in the QuantiFERON-TB in-Tube-assay. Blood from 24 adults with latent tuberculosis infection was added to one standard set of QuantiFERON tubes and one further set containing teriflunomide. Teriflunomide resulted in a change in QuantiFERON results from positive to negative in four patients with a marked reduction in interferon-γ. Our data indicated that results from QuantiFERON in patients on teriflunomide therapy should be interpreted with caution.
[Mh] Termos MeSH primário: Crotonatos/metabolismo
Reações Falso-Negativas
Fatores Imunológicos/metabolismo
Testes de Liberação de Interferon-gama/métodos
Linfócitos T/efeitos dos fármacos
Toluidinas/metabolismo
Tuberculose/diagnóstico
[Mh] Termos MeSH secundário: Adulto
Feminino
Seres Humanos
Interferon gama/análise
Interleucina-2/análise
Masculino
Linfócitos T/metabolismo
Fator de Necrose Tumoral alfa/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Crotonates); 0 (IL2 protein, human); 0 (Immunologic Factors); 0 (Interleukin-2); 0 (Toluidines); 0 (Tumor Necrosis Factor-alpha); 1C058IKG3B (teriflunomide); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161006
[St] Status:MEDLINE
[do] DOI:10.1007/s00430-016-0482-x



página 1 de 47 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde