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[PMID]:29332223
[Au] Autor:Togasaki E; Shimizu N; Nagao Y; Kawajiri-Manako C; Shimizu R; Oshima-Hasegawa N; Muto T; Tsukamoto S; Mitsukawa S; Takeda Y; Mimura N; Ohwada C; Takeuchi M; Sakaida E; Iseki T; Yoshitomi H; Ohtsuka M; Miyazaki M; Nakaseko C
[Ad] Endereço:Department of Hematology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan.
[Ti] Título:Long-term efficacy of partial splenic embolization for the treatment of steroid-resistant chronic immune thrombocytopenia.
[So] Source:Ann Hematol;97(4):655-662, 2018 Apr.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Thrombopoietin-receptor agonists have been recently introduced for a second-line treatment of immune thrombocytopenia (ITP). Splenectomy has tended to be avoided because of its complications, but the response rate of splenectomy is 60-80% and it has still been considered for steroid-refractory ITP. We performed partial splenic embolization (PSE) as an alternative to splenectomy. Between 1988 and 2013, 91 patients with steroid-resistant ITP underwent PSE at our hospital, and we retrospectively analyzed the efficacy and long-term outcomes of PSE. The complete response rate (CR, platelets > 100 × 10 /L) was 51% (n = 46), and the overall response rate (CR plus response (R), > 30 × 10 /L) was 84% (n = 76). One year after PSE, 70% of patients remained CR and R. The group with peak platelet count after PSE ≥ 300 × 10 /L (n = 29) exhibited a significantly higher platelet count than the group with platelet count < 300 × 10 /L (n = 40) at any time point after PSE. The failure-free survival (FFS) rates at 1, 5, and 10 years were 78, 56, and 52%, respectively. Second PSE was performed in 20 patients who relapsed (n = 14) or had no response to the initial PSE (n = 6), and the overall response was achieved in 63% patients. There were no PSE-related deaths. These results indicate that PSE is a safe and effective alternative therapy to splenectomy for patients with steroid-resistant ITP as it generates long-term, durable responses.
[Mh] Termos MeSH primário: Embolização Terapêutica
Púrpura Trombocitopênica Idiopática/terapia
Baço/irrigação sanguínea
[Mh] Termos MeSH secundário: Adolescente
Corticosteroides/uso terapêutico
Adulto
Idoso
Idoso de 80 Anos ou mais
Intervalo Livre de Doença
Resistência a Medicamentos
Resistência a Múltiplos Medicamentos
Embolização Terapêutica/efeitos adversos
Feminino
Seguimentos
Hospitais Universitários
Seres Humanos
Japão
Masculino
Meia-Idade
Tamanho do Órgão
Púrpura Trombocitopênica Idiopática/diagnóstico por imagem
Púrpura Trombocitopênica Idiopática/tratamento farmacológico
Púrpura Trombocitopênica Idiopática/patologia
Estudos Retrospectivos
Baço/diagnóstico por imagem
Baço/efeitos dos fármacos
Baço/patologia
Esteroides/uso terapêutico
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Adrenal Cortex Hormones); 0 (Steroids)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180115
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-018-3232-x


  2 / 27414 MEDLINE  
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[PMID]:29214785
[Au] Autor:Jang H; Kim KY; Kim DS
[Ad] Endereço:Department of Pediatrics, Yonsei University College of Medicine, Severance Children's Hospital, Seoul, Korea.
[Ti] Título:Clinical Outcomes of Low-Dose Methotrexate Therapy as a Second-Line Drug for Intravenous Immunoglobulin-Resistant Kawasaki Disease.
[So] Source:Yonsei Med J;59(1):113-118, 2018 Jan.
[Is] ISSN:1976-2437
[Cp] País de publicação:Korea (South)
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Intravenous immunoglobulin (IVIG) is the standard treatment for Kawasaki disease (KD). However, there is still no standard treatment for IVIG-resistant KD. This study aimed to evaluate the efficacy of low-dose methotrexate (MTX) as a treatment for IVIG-resistant KD. MATERIALS AND METHODS: We retrospectively analyzed 10-year data for patients with IVIG-resistant KD who were administered MTX at Severance Children's Hospital. RESULTS: The subjects included 75 patients with KD aged 5 months to 9.2 years who had been administered MTX. Their maximum body temperatures decreased significantly within 24 h of therapy. The patients' C-reactive protein levels were significantly lower 1 week after administering the first dose of MTX than those before treatment. No adverse effect for MTX was observed. CONCLUSION: MTX treatment of IVIG-resistant KD resulted in rapid defervescence, improvement of clinical symptoms, and normalization of acute-phase reactants in all patients. Thus, MTX could be a candidate treatment for IVIG-resistant KD.
[Mh] Termos MeSH primário: Imunoglobulinas Intravenosas/uso terapêutico
Metotrexato/uso terapêutico
Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico
[Mh] Termos MeSH secundário: Proteína C-Reativa/análise
Criança
Pré-Escolar
Vasos Coronários/patologia
Demografia
Relação Dose-Resposta a Droga
Quimioterapia Combinada
Feminino
Seres Humanos
Lactente
Masculino
Metotrexato/administração & dosagem
Síndrome de Linfonodos Mucocutâneos/sangue
Estudos Retrospectivos
Esteroides/uso terapêutico
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Immunoglobulins, Intravenous); 0 (Steroids); 9007-41-4 (C-Reactive Protein); YL5FZ2Y5U1 (Methotrexate)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE
[do] DOI:10.3349/ymj.2018.59.1.113


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[PMID]:28747178
[Au] Autor:Durnas B; Piktel E; Watek M; Wollny T; Gózdz S; Smok-Kalwat J; Niemirowicz K; Savage PB; Bucki R
[Ad] Endereço:Department of Microbiology and Immunology, The Faculty of Health Sciences of the Jan Kochanowski University in Kielce, Kielce, Poland.
[Ti] Título:Anaerobic bacteria growth in the presence of cathelicidin LL-37 and selected ceragenins delivered as magnetic nanoparticles cargo.
[So] Source:BMC Microbiol;17(1):167, 2017 Jul 26.
[Is] ISSN:1471-2180
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Cationic antibacterial peptides (CAPs) and synthetic molecules mimicking the amphiphilic structure of CAPs, such as ceragenins, are promising compounds for the development of new antimicrobials. RESULTS: We tested the in vitro activity of ceragenins CSA-13 and CSA-131 against several anaerobic bacteria including Bacteroides spp. and Clostridium difficile. We compared results to the activity of cathelicidin LL-37, metronidazole and nanosystems developed by attachment of CSA-13 and CSA-131 to magnetic nanoparticles (MNPs). The antibacterial effect was tested using killing assay and modified CLSI broth microdilution assay. Ceragenins CSA-13 and CSA-131 displayed stronger bactericidal activity than LL-37 or metronidazole against all of the tested bacterial strains. Additionally CSA-131 revealed an enhanced ability to prevent the formation of Bacteroides fragilis and Propionibacterium acnes biofilms. CONCLUSIONS: These data confirmed that ceragenins display antimicrobial activity against a broad range of microorganisms including anaerobic bacteria and deserve further investigations as compounds serving to develop new treatment against anaerobic and mixed infections.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Peptídeos Catiônicos Antimicrobianos/farmacologia
Bactérias Anaeróbias/efeitos dos fármacos
Bactérias Anaeróbias/crescimento & desenvolvimento
Nanopartículas de Magnetita/química
Pregnanos/farmacologia
Esteroides/farmacologia
[Mh] Termos MeSH secundário: Antibacterianos/química
Peptídeos Catiônicos Antimicrobianos/química
Pregnanos/química
Esteroides/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Antimicrobial Cationic Peptides); 0 (Magnetite Nanoparticles); 0 (Pregnanes); 0 (Steroids); 0 (ceragenin CSA-13); 143108-26-3 (CAP18 lipopolysaccharide-binding protein)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170728
[St] Status:MEDLINE
[do] DOI:10.1186/s12866-017-1075-6


  4 / 27414 MEDLINE  
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[PMID]:29191846
[Au] Autor:David M; Rangaraju M; Raine A
[Ad] Endereço:The Royal Orthopaedic Hospital, Birmingham, UK michaeldavid@nhs.net.
[Ti] Título:Acquired triggering of the fingers and thumb in adults.
[So] Source:BMJ;359:j5285, 2017 11 30.
[Is] ISSN:1756-1833
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Deformidades Adquiridas da Mão/patologia
Deformidades Articulares Adquiridas/patologia
Tenossinovite/patologia
Polegar/patologia
Dedo em Gatilho/patologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Inglaterra/epidemiologia
Feminino
Deformidades Adquiridas da Mão/etiologia
Deformidades Adquiridas da Mão/cirurgia
Seres Humanos
Injeções Subcutâneas
Liberação da Cápsula Articular/métodos
Deformidades Articulares Adquiridas/etiologia
Deformidades Articulares Adquiridas/cirurgia
Masculino
Meia-Idade
Estudos Observacionais como Assunto
Prevalência
Atenção Primária à Saúde/estatística & dados numéricos
Esteroides/administração & dosagem
Esteroides/uso terapêutico
Tenossinovite/etiologia
Polegar/cirurgia
Dedo em Gatilho/tratamento farmacológico
Dedo em Gatilho/etiologia
Dedo em Gatilho/cirurgia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Steroids)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171202
[St] Status:MEDLINE
[do] DOI:10.1136/bmj.j5285


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[PMID]:28511566
[Au] Autor:Vien LT; Hanh TTH; Hong PT; Thanh NV; Huong TT; Cuong NX; Nam NH; Thung DC; Kiem PV; Minh CV
[Ad] Endereço:a Institute of Marine Biochemistry, Vietnam Academy of Science and Technology (VAST) , Hanoi , Vietnam.
[Ti] Título:Polar steroid derivatives from the Vietnamese starfish Astropecten polyacanthus.
[So] Source:Nat Prod Res;32(1):54-59, 2018 Jan.
[Is] ISSN:1478-6427
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Five polar steroid derivatives, including one new glycosylated polyhydroxysteroid namely polyacanthoside A (1), were isolated from the water-soluble materials from the MeOH extract of the Vietnamese starfish Astropecten polyacanthus using various chromatographic separations. The structure elucidation was confirmed by spectroscopic experiments such as HR-ESI-MS, 1D and 2D NMR. Among the isolated compounds, (20R,24S)-3ß,6α,8,15ß,24-pentahydroxy-5α-cholestane (3) showed significant cytotoxic effect against five human cancer cell lines as HepG2, KB, LNCaP, MCF7 and SK-Mel2 with the IC values from 18.03 ± 2.63 to 21.59 ± 3.23 µM.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Estrelas-do-Mar/química
Esteroides/química
Esteroides/farmacologia
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/química
Linhagem Celular Tumoral
Ensaios de Seleção de Medicamentos Antitumorais/métodos
Seres Humanos
Concentração Inibidora 50
Espectroscopia de Ressonância Magnética
Estrutura Molecular
Espectrometria de Massas por Ionização por Electrospray
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Steroids)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170518
[St] Status:MEDLINE
[do] DOI:10.1080/14786419.2017.1329733


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[PMID]:28449695
[Au] Autor:Ness T; Boehringer D; Heinzelmann S
[Ad] Endereço:Eye Center, Medical Center, University of Freiburg, Faculty of Medicine, Killianstr. 5, 79106, Freiburg, Germany. thomas.ness@uniklinik-freiburg.de.
[Ti] Título:Intermediate uveitis: pattern of etiology, complications, treatment and outcome in a tertiary academic center.
[So] Source:Orphanet J Rare Dis;12(1):81, 2017 Apr 27.
[Is] ISSN:1750-1172
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Patients with intermediate uveitis (IU) represent a heterogenous group characterized by a wide spectrum of etiologies and regional differences. Aim of the study was to analyze the characteristics of patients with IU examined in an academic center in Germany. METHODS: We conducted a retrospective analysis of the clinical records of all patients with intermediate uveitis referred to the Eye Center, University of Freiburg from 2007 to 2014. Diagnosis followed the Standardization in Uveitis Nomenclature (SUN) criteria. Data analysis included: etiology of IU, demographics, complications, treatment and visual acuity. RESULTS: We identified 159 patients with intermediate uveitis during that period. Mean age at diagnosis was 35 years. Most are female (64%), and the mean duration of IU was 6.1 years (range 1 month - 35 years). Etiology of IU was idiopathic in 59%. Multiple sclerosis (MS) (20%) and sarcoidosis (10%) were frequent systemic causes of IU. Other etiologies including infectious diseases (tuberculosis, borreliosis) or immune-mediated conditions (eg, after vaccination) were present in 11%. The pattern of complications included macular edema (CME) (36%), cataract (24%), secondary glaucoma (7%), and epiretinal membrane formation (19%). Periphlebitis and optic neuritis were more frequent in conjunction with MS. Treatment comprised local and systemic steroids, immunosuppressive agents, biologics, and surgery. Best corrected visual acuity was better than 20/25 in 60% of the eyes after more than 10 years of follow-up. CONCLUSIONS: In our German academic center, most IU cases were idiopathic or associated with MS or sarcoidosis. In contrast to other countries, infectious cases were rare. Patients' overall visual prognosis is favorable even when the duration of IU has been long and and despite numerous complications.
[Mh] Termos MeSH primário: Catarata/etiologia
Glaucoma/etiologia
Imunossupressores/uso terapêutico
Esclerose Múltipla/complicações
Sarcoidose/complicações
Uveíte Intermediária
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Catarata/fisiopatologia
Criança
Pré-Escolar
Feminino
Glaucoma/fisiopatologia
Seres Humanos
Edema Macular/etiologia
Edema Macular/fisiopatologia
Masculino
Meia-Idade
Esclerose Múltipla/fisiopatologia
Estudos Retrospectivos
Sarcoidose/fisiopatologia
Esteroides/uso terapêutico
Resultado do Tratamento
Uveíte Intermediária/complicações
Uveíte Intermediária/tratamento farmacológico
Uveíte Intermediária/etiologia
Uveíte Intermediária/fisiopatologia
Acuidade Visual/fisiologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Immunosuppressive Agents); 0 (Steroids)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1186/s13023-017-0638-9


  7 / 27414 MEDLINE  
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[PMID]:29310026
[Au] Autor:Shi YK; Wang B; Shi XL; Zhao YD; Yu B; Liu HM
[Ad] Endereço:Key Laboratory of Advanced Drug Preparation Technologies (Zhengzhou University), Ministry of Education, PR China; Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, PR China; School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, PR China;
[Ti] Título:Synthesis and biological evaluation of new steroidal pyridines as potential anti-prostate cancer agents.
[So] Source:Eur J Med Chem;145:11-22, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:A series of new steroidal pyridines have been synthesized through the based-promoted three-component reaction and preliminarily evaluated for their antiproliferative activity against different types of cancer cell lines. SARs studies showed that the heterocyclic rings attached to the 4-position of the pyridine ring were preferred over the phenyl rings for the activity. Among these compounds, the most potent compound exhibited good growth inhibition against all the tested cancer cells, especially for PC-3 cells with an IC value of 1.55 µM. Further mechanistic studies revealed that the most potent compound inhibited colony formation, migration and evasion of PC-3 cells in a concentration-dependent manner as well as induced apoptosis of PC-3 cells possibly through the mitochondria-related apoptotic pathways. Caspase-3/-9 and PARP were activated, finally leading to the apoptosis of PC-3 cells. For the androgen-sensitive (AR ) prostate cancer cell line LNCaP, the most potent compound was less potent than abiraterone with the IC value of 8.48 and 3.29 µM, respectively. The most potent compound could be used as a starting point for the development of new steroidal heterocycles with improved anticancer potency and selectivity. The synthesized steroidal pyridines contain the functional -OEt and CN groups, which could be used for further modifications for the construction of the steroid library.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Piridinas/farmacologia
Esteroides/farmacologia
[Mh] Termos MeSH secundário: Antineoplásicos/síntese química
Antineoplásicos/química
Apoptose/efeitos dos fármacos
Ciclo Celular/efeitos dos fármacos
Movimento Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Relação Dose-Resposta a Droga
Ensaios de Seleção de Medicamentos Antitumorais
Seres Humanos
Estrutura Molecular
Piridinas/síntese química
Piridinas/química
Esteroides/síntese química
Esteroides/química
Relação Estrutura-Atividade
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Pyridines); 0 (Steroids)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180109
[St] Status:MEDLINE


  8 / 27414 MEDLINE  
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[PMID]:27778092
[Au] Autor:Dossier C; Lapidus N; Bayer F; Sellier-Leclerc AL; Boyer O; de Pontual L; May A; Nathanson S; Orzechowski C; Simon T; Carrat F; Deschênes G
[Ad] Endereço:Service de Néphrologie Pédiatrique, Hôpital Robert-Debré, APHP, Paris, France. claire.dossier@aphp.fr.
[Ti] Título:Epidemiology of idiopathic nephrotic syndrome in children: endemic or epidemic?
[So] Source:Pediatr Nephrol;31(12):2299-2308, 2016 Dec.
[Is] ISSN:1432-198X
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The etiology of idiopathic nephrotic syndrome (INS) remains partially unknown. Viral infections have been reported to be associated with INS onset and relapse. The aim of this study was to describe the epidemiology of a population-based cohort of children with INS and propose a spatiotemporal analysis. METHODS: All children aged 6 months to 15 years with INS onset between December 2007 and May 2010 and living in the Paris area were included in a prospective multicenter study. Demographic and clinical features at diagnosis and 2 years were collected. RESULTS: INS was diagnosed in 188 children, 93 % of whom were steroid sensitive. Annual incidence was 3.35/100,000 children. Standardized incidence ratio (SIR) was higher in one of the eight counties: Seine-Saint-Denis, with SIR 1.43 [95 % confidence interval (CI) 1.02-1.95]. A spatial cluster was further identified with higher SIR 1.36 (95 % CI 1.09-1.67). Temporal analysis within this overincidence area showed seasonal variation, with a peak during the winter period (p <0.01). In addition, partition of the Paris area into quintiles of the population showed that the average delay of occurrence, with regard to the first study case, followed a longitudinal progression (p <0.0001). CONCLUSION: The clustering of cases, the seasonal variation within this particular area, and the progression over the Paris area altogether suggest that INS may occur on an epidemic mode.
[Mh] Termos MeSH primário: Síndrome Nefrótica/epidemiologia
[Mh] Termos MeSH secundário: Adolescente
Fatores Etários
Criança
Pré-Escolar
Análise por Conglomerados
Estudos de Coortes
Doenças Endêmicas
Epidemias
Feminino
Seres Humanos
Incidência
Lactente
Masculino
Síndrome Nefrótica/tratamento farmacológico
Síndrome Nefrótica/virologia
Paris/epidemiologia
Estudos Prospectivos
Estações do Ano
Fatores Socioeconômicos
Esteroides/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Steroids)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE


  9 / 27414 MEDLINE  
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[PMID]:29300865
[Au] Autor:Fan J; Wang K; Zirkin B; Papadopoulos V
[Ad] Endereço:Research Institute of the McGill University Health Centre and Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
[Ti] Título:CRISPR/Cas9‒Mediated Tspo Gene Mutations Lead to Reduced Mitochondrial Membrane Potential and Steroid Formation in MA-10 Mouse Tumor Leydig Cells.
[So] Source:Endocrinology;159(2):1130-1146, 2018 02 01.
[Is] ISSN:1945-7170
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The outer mitochondrial membrane translocator protein (TSPO) binds cholesterol with high affinity and is involved in mediating its delivery into mitochondria, the rate-limiting step in hormone-induced steroidogenesis. Specific ligand binding to TSPO has been shown to initiate steroid formation. However, recent studies of the genetic deletion of Tspo have provided conflicting results. Here, we address and extend previous studies by examining the effects of Tspo-specific mutations on steroid formation in hormone- and cyclic adenosine monophosphate (cAMP)-responsive MA-10 cells, using the CRISPR/Cas9 system. Two mutant subcell lines, nG1 and G2G, each carrying a Tspo exon2-specific genome modification, and two control subcell lines, G1 and HH, each carrying a wild-type Tspo, were produced. In response to dibutyryl cAMP, the nG1 and G2G cells produced progesterone at levels significantly lower than those produced by the corresponding control cells G1 and HH. Neutral lipid homeostasis, which provides free cholesterol for steroid biosynthesis, was altered significantly in the Tspo mutant cells. Interestingly, the mitochondrial membrane potential (ΔΨm) of the Tspo mutant cells was significantly reduced compared with that of the control cells, likely because of TSPO interactions with the voltage-dependent anion channel and tubulin at the outer mitochondrial membrane. Steroidogenic acute regulatory protein (STAR) expression was induced in nG1 cells, suggesting that reduced TSPO affected STAR synthesis and/or processing. Taken together, these results provide further evidence for the critical role of TSPO in steroid biosynthesis and suggest that it may function at least in part via its regulation of ΔΨm and effects on STAR.
[Mh] Termos MeSH primário: Sistemas CRISPR-Cas/genética
Hormônios Esteroides Gonadais/biossíntese
Células Intersticiais do Testículo/metabolismo
Potencial da Membrana Mitocondrial/genética
Mutagênese Sítio-Dirigida
Mutação
Receptores de GABA/genética
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Tumor de Células de Leydig/genética
Tumor de Células de Leydig/metabolismo
Tumor de Células de Leydig/patologia
Masculino
Camundongos
Mutagênese Sítio-Dirigida/métodos
Fosfoproteínas/genética
Fosfoproteínas/metabolismo
Esteroides/biossíntese
Neoplasias Testiculares/genética
Neoplasias Testiculares/metabolismo
Neoplasias Testiculares/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bzrp protein, mouse); 0 (Gonadal Steroid Hormones); 0 (Phosphoproteins); 0 (Receptors, GABA); 0 (Steroids); 0 (steroidogenic acute regulatory protein)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180105
[St] Status:MEDLINE
[do] DOI:10.1210/en.2017-03065


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[PMID]:27776205
[Au] Autor:Singh R; Bansal R
[Ad] Endereço:University Institute of Pharmaceutical Sciences, Panjab University , Chandigarh 160 014, India.
[Ti] Título:Investigations on 16-Arylideno Steroids as a New Class of Neuroprotective Agents for the Treatment of Alzheimer's and Parkinson's Diseases.
[So] Source:ACS Chem Neurosci;8(1):186-200, 2017 01 18.
[Is] ISSN:1948-7193
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Neuroinflammatory mechanisms mediated by activated glial and cytokines (TNF-α, IL-1ß) might contribute to neuronal degeneration leading to Alzheimer's (AD) and Parkinson's disease (PD). Lipopolysaccharide (LPS) is an inflammogen derived from the cell wall of Gram-negative bacteria, which promotes neuroinflammation and subsequent neurodegeneration. Dehydroepiandrosterone (DHEA) and testosterone have been reported as neuroprotective steroids useful for the treatment of various neurodegenerative disorders. In the present study, several 16-arylidene steroidal derivatives have been evaluated as neuroprotective agents in LPS-treated animal models. It was observed that 16-arylidene steroidal derivatives 1a-d and 6a-h considerably improve LPS-induced learning, memory, and movement deficits in animal models. Biochemical estimations of brain serum of treated animals revealed suppression of oxidative and nitrosative stress, acetylcholinesterase activity, and reduction in TNF-α levels, which were induced through LPS mediated neuroinflammatory mechanisms leading to neurodegeneration of brain. Of all the steroidal derivatives, 16-(4-pyridylidene) steroid 1c and its 4-aza analogue 6c were found to be the most active neuroprotective agents and produced effects comparable to standard drug celecoxib at a much lower dose and better than dexamethasone at the same dose in terms of behavioral, biochemical, and molecular aspects.
[Mh] Termos MeSH primário: Encefalite/tratamento farmacológico
Fármacos Neuroprotetores/química
Fármacos Neuroprotetores/uso terapêutico
Esteroides/uso terapêutico
[Mh] Termos MeSH secundário: Acetilcolinesterase/metabolismo
Análise de Variância
Animais
Catatonia/etiologia
Citocinas/metabolismo
Modelos Animais de Doenças
Encefalite/induzido quimicamente
Encefalite/complicações
Glutationa/metabolismo
Peroxidação de Lipídeos/efeitos dos fármacos
Lipopolissacarídeos/toxicidade
Masculino
Aprendizagem em Labirinto/efeitos dos fármacos
Camundongos
Modelos Moleculares
Simulação de Acoplamento Molecular
Fármacos Neuroprotetores/síntese química
Ratos
Esteroides/síntese química
Esteroides/química
Superóxido Dismutase/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cytokines); 0 (Lipopolysaccharides); 0 (Neuroprotective Agents); 0 (Steroids); EC 1.15.1.1 (Superoxide Dismutase); EC 3.1.1.7 (Acetylcholinesterase); GAN16C9B8O (Glutathione)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1021/acschemneuro.6b00313



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