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  1 / 20 MEDLINE  
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[PMID]:27600150
[Au] Autor:Fleseriu M; Castinetti F
[Ad] Endereço:Departments of Medicine and Neurological Surgery, and Northwest Pituitary Center, Oregon Health & Science University, Mail Code: CH8N, 3303 SW Bond Ave, Portland, OR, 97239, USA. fleseriu@ohsu.edu.
[Ti] Título:Updates on the role of adrenal steroidogenesis inhibitors in Cushing's syndrome: a focus on novel therapies.
[So] Source:Pituitary;19(6):643-653, 2016 Dec.
[Is] ISSN:1573-7403
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Endogenous Cushing's syndrome (CS) is a rare disease that results from exposure to high levels of cortisol; Cushing's disease (CD) is the most frequent form of CS. Patients with CS suffer from a variety of comorbidities that increase the risk of mortality. Surgical resection of the disease-causing lesion is generally the first-line treatment of CS. However, some patients may not be eligible for surgery due to comorbidities, and approximately 25 % of patients, especially those with CD, have recurrent disease. For these patients, adrenal steroidogenesis inhibitors may control cortisol elevation and subsequent symptomatology. CS is rare overall, and clinical studies of adrenal steroidogenesis inhibitors are often small and, in many cases, data are limited regarding the efficacy and safety of these treatments. Our aim was to better characterize the profiles of efficacy and safety of currently available adrenal steroidogenesis inhibitors, including drugs currently in development. METHODS: We performed a systematic review of the literature regarding adrenal steroidogenesis inhibitors, focusing on novel drugs. RESULTS: Currently available adrenal steroidogenesis inhibitors, including ketoconazole, metyrapone, etomidate, and mitotane, have variable efficacy and significant side effects, and none are approved by the US Food and Drug Administration for CS. Therefore, there is a clear need for novel, prospectively studied agents that have greater efficacy and a low rate of adverse side effects. Efficacy and safety data of current and emerging adrenal steroidogenesis inhibitors, including osilodrostat (LCI699) and levoketoconazole (COR-003), show promising results that will have to be confirmed in larger-scale phase 3 studies (currently ongoing). CONCLUSIONS: The management of CS, and particularly CD, remains challenging. Adrenal steroidogenesis inhibitors can be of major interest to control the hypercortisolism at any time point, either before or after surgery, as discussed in this review.
[Mh] Termos MeSH primário: Síndrome de Cushing/tratamento farmacológico
Inibidores da Síntese de Esteroides/uso terapêutico
[Mh] Termos MeSH secundário: Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Steroid Synthesis Inhibitors)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170405
[Lr] Data última revisão:
170405
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160908
[St] Status:MEDLINE


  2 / 20 MEDLINE  
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[PMID]:27515536
[Au] Autor:Bernini G; Tricò D
[Ad] Endereço:Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, Pisa, 56126 Italy. giampaolo.bernini@med.unipi.it.
[Ti] Título:Cushing's Syndrome and Steroid Dementia.
[So] Source:Recent Pat Endocr Metab Immune Drug Discov;10(1):50-55, 2016.
[Is] ISSN:1872-2148
[Cp] País de publicação:United Arab Emirates
[La] Idioma:eng
[Ab] Resumo:Cushing's Syndrome (CS) is associated with a specific spectrum of dementia-like symptoms, including psychiatric disorders, such as major depression, anxiety and mania, and neurocognitive alterations, like impairment of memory and concentration. This pattern of clinical complications, which significantly impair the health-related quality of life of CS patients, is sometimes referred to as "steroid dementia syndrome" (SDS). The SDS is the result of anatomical and functional anomalies in brain areas involved in the processing of emotion and cognition, which are only partially restored after the biochemical remission of the disease. Therefore, periodical neuropsychiatric evaluations are recommended in all CS patients, and a long-term follow-up is required after normalization of hypercortisolism. Recent evidences demonstrate that three classes of drugs (glucocorticoid receptor antagonists, steroidogenesis inhibitors, and pituitary tumor-targeted drugs), which are used for medical treatment of CS, can rapidly relief neuropsychiatric symptoms of SDS. Furthermore, several psychoactive medications have demonstrated effectiveness in the treatment of symptoms induced by the acute or chronic glucocosteroid administration. In this paper, a review of the current and future patents for the treatment and prevention of CS and SDS will be presented.
[Mh] Termos MeSH primário: Encéfalo/metabolismo
Cognição
Síndrome de Cushing/complicações
Demência/etiologia
Emoções
Hidrocortisona/metabolismo
[Mh] Termos MeSH secundário: Animais
Encéfalo/efeitos dos fármacos
Encéfalo/fisiopatologia
Síndrome de Cushing/tratamento farmacológico
Síndrome de Cushing/metabolismo
Demência/tratamento farmacológico
Demência/metabolismo
Demência/psicologia
Descoberta de Drogas
Antagonistas de Hormônios/uso terapêutico
Seres Humanos
Terapia de Alvo Molecular
Qualidade de Vida
Receptores de Glucocorticoides/antagonistas & inibidores
Receptores de Glucocorticoides/metabolismo
Transdução de Sinais/efeitos dos fármacos
Esteroide Hidroxilases/antagonistas & inibidores
Esteroide Hidroxilases/metabolismo
Inibidores da Síntese de Esteroides/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Hormone Antagonists); 0 (Receptors, Glucocorticoid); 0 (Steroid Synthesis Inhibitors); EC 1.14.- (Steroid Hydroxylases); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170314
[Lr] Data última revisão:
170314
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160813
[St] Status:MEDLINE


  3 / 20 MEDLINE  
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[PMID]:26782012
[Au] Autor:Oda H; Mori A; Shono S; Onozawa E; Sako T
[Ad] Endereço:School of Veterinary Nursing and Technology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University, 1-7-1 Kyonancho, Musashino, Tokyo 180-8602, Japan.
[Ti] Título:The effect of 1 year of trilostane treatment on peripheral lymphocyte subsets in dogs with pituitary-dependent hyperadrenocorticism.
[So] Source:J Vet Med Sci;78(5):851-4, 2016 Jun 01.
[Is] ISSN:1347-7439
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:This study investigated the changes in lymphocyte subsets during the trilostane medication of Pituitary-dependent hyperadrenocorticism (PDH) dogs. The cortisol level and lymphocyte subsets of eight dogs with PDH were monitored 0, 1, 3, 6, 9 and 12 months after the initiation of trilostane treatment. White blood cells (WBC), lymphocytes, CD3(+) (T lymphocyte), CD4(+) (helper T lymphocyte), CD8(+) (cytotoxic T lymphocyte) and CD21(+) (B lymphocyte) cells were measured. Although the post-ACTH stimulation test cortisol level was significantly lower during trilostane treatment, changes in the CD3(+), CD4(+), CD8(+) and CD21(+) counts were not observed. Meanwhile, significant decrease was observed in WBC counts during trilostane treatment. These indicate that long-term trilostane treatment has little effect on the lymphocyte subsets in PDH dogs.
[Mh] Termos MeSH primário: Hiperfunção Adrenocortical/veterinária
Di-Hidrotestosterona/análogos & derivados
Doenças do Cão/tratamento farmacológico
Subpopulações de Linfócitos/efeitos dos fármacos
Inibidores da Síntese de Esteroides/uso terapêutico
[Mh] Termos MeSH secundário: Hiperfunção Adrenocortical/tratamento farmacológico
Hiperfunção Adrenocortical/imunologia
Hormônio Adrenocorticotrópico/farmacologia
Animais
Contagem de Linfócito CD4/veterinária
Linfócitos T CD8-Positivos/efeitos dos fármacos
Di-Hidrotestosterona/uso terapêutico
Doenças do Cão/imunologia
Cães
Feminino
Hidrocortisona/sangue
Masculino
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Steroid Synthesis Inhibitors); 08J2K08A3Y (Dihydrotestosterone); 9002-60-2 (Adrenocorticotropic Hormone); L0FPV48Q5R (trilostane); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170608
[Lr] Data última revisão:
170608
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160120
[St] Status:MEDLINE
[do] DOI:10.1292/jvms.15-0410


  4 / 20 MEDLINE  
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[PMID]:26727040
[Au] Autor:Jahn H
[Ad] Endereço:Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany. Electronic address: jahn@uke.uni-hamburg.de.
[Ti] Título:Steroid-synthesis inhibition in depression: a good idea?
[So] Source:Lancet Psychiatry;3(2):92-3, 2016 Feb.
[Is] ISSN:2215-0374
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Depressão
Inibidores da Síntese de Esteroides
[Mh] Termos MeSH secundário: Células Cultivadas
Depressão Química
Transtorno Depressivo
Hidrocortisona
Cinética
Progesterona
Esteroides
[Pt] Tipo de publicação:COMMENT; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Steroid Synthesis Inhibitors); 0 (Steroids); 4G7DS2Q64Y (Progesterone); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:160207
[Lr] Data última revisão:
160207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160105
[St] Status:MEDLINE


  5 / 20 MEDLINE  
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[PMID]:26116295
[Au] Autor:Geynisman DM; Ross EA; Plimack ER
[Ad] Endereço:Medical Oncology, Fox Chase Cancer Center Temple Health, Philadelphia, PA, USA.
[Ti] Título:Osteoclast inhibitors in advanced prostate cancer: does the benefit extend beyond skeletal-related events?
[So] Source:Eur Urol;68(4):578-80, 2015 Oct.
[Is] ISSN:1873-7560
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Mh] Termos MeSH primário: Acetato de Abiraterona/uso terapêutico
Antineoplásicos Hormonais/uso terapêutico
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Conservadores da Densidade Óssea/uso terapêutico
Neoplasias Ósseas/tratamento farmacológico
Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico
Inibidores da Síntese de Esteroides/uso terapêutico
[Mh] Termos MeSH secundário: Seres Humanos
Masculino
[Pt] Tipo de publicação:COMMENT; EDITORIAL
[Nm] Nome de substância:
0 (Antineoplastic Agents, Hormonal); 0 (Bone Density Conservation Agents); 0 (Steroid Synthesis Inhibitors); EM5OCB9YJ6 (Abiraterone Acetate)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:150904
[Lr] Data última revisão:
150904
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150628
[St] Status:MEDLINE


  6 / 20 MEDLINE  
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[PMID]:26002041
[Au] Autor:Midzak A; Denora N; Laquintana V; Cutrignelli A; Lopedota A; Franco M; Altomare CD; Papadopoulos V
[Ad] Endereço:The Research Institute of the McGill University Health Centre, Departments of Medicine, Biochemistry, and Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1A4, Canada.
[Ti] Título:2-Phenylimidazo[1,2-a]pyridine-containing ligands of the 18-kDa translocator protein (TSPO) behave as agonists and antagonists of steroidogenesis in a mouse leydig tumor cell line.
[So] Source:Eur J Pharm Sci;76:231-7, 2015 Aug 30.
[Is] ISSN:1879-0720
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Ligands of 18-kDa translocator protein (TSPO) are known for their ability to potently and dose-dependently stimulate steroid biosynthesis in steroidogenic cells. In this study, we investigated a number of 2-phenyl-imidazo[1,2-a]pyridine acetamide derivatives, analogs of alpidem, for their ability to bind TSPO and to affect steroidogenesis in a mouse Leydig tumor cell line. We observed that not only some compounds behaved as agonists, stimulating steroidogenesis (e.g., 3 and 4) with EC50 values (15.9 and 6.99µM) close to that determined for FGIN-1-27 used as positive control (7.24µM), but two compounds, namely 5 and 6, which on the other hand are the most lipophilic ones in the investigated series, behaved as antagonists, by significantly inhibiting steroid production at concentrations at least twenty times lower than the cytotoxic ones. To our surprise, the newly synthesized compound 3, which is a strict analog of alpidem bearing at the para position of the 2-phenyl group a methoxy group instead of chlorine, achieved a ten-fold stimulation of the steroid production (for comparison FGIN-1-27 achieved 1.6-fold stimulation). Within the limits of the examined property space, some unprecedented SARs were unveiled, which can help in understanding the key molecular factors underlying the transition from agonism to antagonism in the steroidogenesis process. Besides the substitution pattern and the physicochemical features (mainly hydrogen bonding potential) of the substituents at the positions C(6) and C(8) of the imidazo[1,2-a]pyridine nucleus, and at the para position of the 2-phenyl group, the structure-activity relationship analysis suggested lipophilicity, whose increase seems to be generally related to steroidogenesis inhibition, and steric hindrance, which appeared as a stimulation-limiting factor, as two main properties to control in the design or optimization of novel imidazo[1,2-a]pyridine-based TSPO ligands endowed with potential in modulating the steroidogenesis process.
[Mh] Termos MeSH primário: Antineoplásicos Hormonais/farmacologia
Antagonistas de Hormônios/farmacologia
Imidazóis/farmacologia
Tumor de Células de Leydig/tratamento farmacológico
Neoplasias Hormônio-Dependentes/tratamento farmacológico
Piridinas/farmacologia
Receptores de GABA/efeitos dos fármacos
Inibidores da Síntese de Esteroides/farmacologia
Neoplasias Testiculares/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antineoplásicos Hormonais/síntese química
Linhagem Celular Tumoral
Relação Dose-Resposta a Droga
Antagonistas de Hormônios/síntese química
Ligações de Hidrogênio
Imidazóis/síntese química
Tumor de Células de Leydig/metabolismo
Tumor de Células de Leydig/patologia
Ligantes
Masculino
Camundongos
Estrutura Molecular
Neoplasias Hormônio-Dependentes/metabolismo
Neoplasias Hormônio-Dependentes/patologia
Piridinas/síntese química
Receptores de GABA/metabolismo
Inibidores da Síntese de Esteroides/síntese química
Relação Estrutura-Atividade
Neoplasias Testiculares/metabolismo
Neoplasias Testiculares/patologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents, Hormonal); 0 (Bzrp protein, mouse); 0 (Hormone Antagonists); 0 (Imidazoles); 0 (Ligands); 0 (Pyridines); 0 (Receptors, GABA); 0 (Steroid Synthesis Inhibitors); I93SC245QZ (alpidem)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:150608
[Lr] Data última revisão:
150608
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150524
[St] Status:MEDLINE


  7 / 20 MEDLINE  
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Registro de Ensaios Clínicos
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[PMID]:25985882
[Au] Autor:Saad F; Shore N; Van Poppel H; Rathkopf DE; Smith MR; de Bono JS; Logothetis CJ; de Souza P; Fizazi K; Mulders PF; Mainwaring P; Hainsworth JD; Beer TM; North S; Fradet Y; Griffin TA; De Porre P; Londhe A; Kheoh T; Small EJ; Scher HI; Molina A; Ryan CJ
[Ad] Endereço:University of Montréal, Montréal, Québec, Canada. Electronic address: fredsaad@videotron.ca.
[Ti] Título:Impact of bone-targeted therapies in chemotherapy-naïve metastatic castration-resistant prostate cancer patients treated with abiraterone acetate: post hoc analysis of study COU-AA-302.
[So] Source:Eur Urol;68(4):570-7, 2015 Oct.
[Is] ISSN:1873-7560
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Metastatic castration-resistant prostate cancer (mCRPC) often involves bone, and bone-targeted therapy (BTT) has become part of the overall treatment strategy. OBJECTIVE: Investigation of outcomes for concomitant BTT in a post hoc analysis of the COU-AA-302 trial, which demonstrated an overall clinical benefit of abiraterone acetate (AA) plus prednisone over placebo plus prednisone in asymptomatic or mildly symptomatic chemotherapy-naïve mCRPC patients. DESIGN, SETTING, AND PARTICIPANTS: This report describes the third interim analysis (prespecified at 55% overall survival [OS] events) for the COU-AA-302 trial. INTERVENTION: Patients were grouped by concomitant BTT use or no BTT use. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Radiographic progression-free survival and OS were coprimary end points. This report describes the third interim analysis (prespecified at 55% OS events) and involves patients treated with or without concomitant BTT during the COU-AA-302 study. Median follow-up for OS was 27.1 mo. Median time-to-event variables with 95% confidence intervals (CIs) were estimated using the Kaplan-Meier method. Adjusted hazard ratios (HRs), 95% CIs, and p values for concomitant BTT versus no BTT were obtained via Cox models. RESULTS AND LIMITATIONS: While the post hoc nature of the analysis is a limitation, superiority of AA and prednisone versus prednisone alone was demonstrated for clinical outcomes with or without BTT use. Compared with no BTT use, concomitant BTT significantly improved OS (HR 0.75; p=0.01) and increased the time to ECOG deterioration (HR 0.75; p<0.001) and time to opiate use for cancer-related pain (HR 0.80; p=0.036). The safety profile of concomitant BTT with AA was similar to that reported for AA in the overall intent-to-treat population. Osteonecrosis of the jaw (all grade 1/2) with concomitant BTT use was reported in <3% of patients. CONCLUSIONS: AA with concomitant BTT was safe and well tolerated in men with chemotherapy-naïve mCRPC. The benefits of AA on clinical outcomes were increased with concomitant BTT. PATIENT SUMMARY: Treatment of advanced prostate cancer often includes bone-targeted therapy. This post hoc analysis showed that in patients with advanced prostate cancer who were treated with abiraterone acetate and prednisone in combination with bone-targeted therapy, there was a continued trend in prolongation of life when compared with patients treated with prednisone alone. TRIAL REGISTRATION: ClinicalTrials.gov NCT00887198.
[Mh] Termos MeSH primário: Acetato de Abiraterona/uso terapêutico
Antineoplásicos Hormonais/uso terapêutico
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Conservadores da Densidade Óssea/uso terapêutico
Neoplasias Ósseas/tratamento farmacológico
Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico
Inibidores da Síntese de Esteroides/uso terapêutico
[Mh] Termos MeSH secundário: Acetato de Abiraterona/efeitos adversos
Idoso
Antineoplásicos Hormonais/efeitos adversos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia
Conservadores da Densidade Óssea/efeitos adversos
Neoplasias Ósseas/mortalidade
Neoplasias Ósseas/secundário
Ensaios Clínicos Fase III como Assunto
Intervalo Livre de Doença
Seres Humanos
Estimativa de Kaplan-Meier
Masculino
Meia-Idade
Estudos Multicêntricos como Assunto
Razão de Chances
Prednisona/uso terapêutico
Modelos de Riscos Proporcionais
Neoplasias de Próstata Resistentes à Castração/mortalidade
Neoplasias de Próstata Resistentes à Castração/patologia
Ensaios Clínicos Controlados Aleatórios como Assunto
Estudos Retrospectivos
Fatores de Risco
Inibidores da Síntese de Esteroides/efeitos adversos
Fatores de Tempo
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antineoplastic Agents, Hormonal); 0 (Bone Density Conservation Agents); 0 (Steroid Synthesis Inhibitors); EM5OCB9YJ6 (Abiraterone Acetate); VB0R961HZT (Prednisone)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:170930
[Lr] Data última revisão:
170930
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150520
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE


  8 / 20 MEDLINE  
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[PMID]:25865060
[Au] Autor:Lu K
[Ad] Endereço:Division of Urology, Department of Surgery, E-Da Hospital, Kaohsiung City, Taiwan, Republic of China; School of Medicine, I-Shou University, Kaohsiung City, Taiwan, Republic of China. Electronic address: kevinlu0620@mail2000.com.tw.
[Ti] Título:Re: Arun A. Azad, Bernhard J. Eigl, Raya Leibowitz-Amit, et al. Outcomes with abiraterone acetate in metastatic castration-resistant prostate cancer patients who have poor performance status. Eur Urol 2015;67:441-7.
[So] Source:Eur Urol;68(3):e55-6, 2015 Sep.
[Is] ISSN:1873-7560
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Mh] Termos MeSH primário: Acetato de Abiraterona/uso terapêutico
Antineoplásicos Hormonais/uso terapêutico
Inibidores das Enzimas do Citocromo P-450/uso terapêutico
Nível de Saúde
Neoplasias Hormônio-Dependentes/tratamento farmacológico
Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico
Inibidores da Síntese de Esteroides/uso terapêutico
[Mh] Termos MeSH secundário: Seres Humanos
Masculino
[Pt] Tipo de publicação:COMMENT; LETTER
[Nm] Nome de substância:
0 (Antineoplastic Agents, Hormonal); 0 (Cytochrome P-450 Enzyme Inhibitors); 0 (Steroid Synthesis Inhibitors); EM5OCB9YJ6 (Abiraterone Acetate)
[Em] Mês de entrada:1512
[Cu] Atualização por classe:150818
[Lr] Data última revisão:
150818
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150414
[St] Status:MEDLINE


  9 / 20 MEDLINE  
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[PMID]:25864159
[Au] Autor:Azad AA; Chi KN
[Ad] Endereço:Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada.
[Ti] Título:Reply to Kevin Lu's letter to the editor re: Arun A. Azad, Bernhard J. Eigl, Raya Leibowitz-Amit, et al. outcomes with abiraterone acetate in metastatic castration-resistant prostate cancer patients who have poor performance status. Eur Urol 2015;67:441-7.
[So] Source:Eur Urol;68(3):e57-8, 2015 Sep.
[Is] ISSN:1873-7560
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Mh] Termos MeSH primário: Acetato de Abiraterona/uso terapêutico
Antineoplásicos Hormonais/uso terapêutico
Inibidores das Enzimas do Citocromo P-450/uso terapêutico
Nível de Saúde
Neoplasias Hormônio-Dependentes/tratamento farmacológico
Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico
Inibidores da Síntese de Esteroides/uso terapêutico
[Mh] Termos MeSH secundário: Seres Humanos
Masculino
[Pt] Tipo de publicação:COMMENT; LETTER
[Nm] Nome de substância:
0 (Antineoplastic Agents, Hormonal); 0 (Cytochrome P-450 Enzyme Inhibitors); 0 (Steroid Synthesis Inhibitors); EM5OCB9YJ6 (Abiraterone Acetate)
[Em] Mês de entrada:1512
[Cu] Atualização por classe:150818
[Lr] Data última revisão:
150818
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150413
[St] Status:MEDLINE


  10 / 20 MEDLINE  
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[PMID]:25863445
[Au] Autor:Bayer J; Rune G; Schultz H; Tobia MJ; Mebes I; Katzler O; Sommer T
[Ad] Endereço:Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: j.bayer@uke.de.
[Ti] Título:The effect of estrogen synthesis inhibition on hippocampal memory.
[So] Source:Psychoneuroendocrinology;56:213-25, 2015 Jun.
[Is] ISSN:1873-3360
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:17-Beta-estradiol (E2) facilitates long term-potentiation (LTP) and increases spine synapse density in hippocampal neurons of ovariectomized rodents. Consistent with these beneficial effects on the cellular level, E2 improves hippocampus-dependent memory. A prominent approach to study E2 effects in rodents is the inhibition of its synthesis by letrozole, which reduces LTPs and spine synapse density. In the current longitudinal functional magnetic resonance imaging (fMRI) study, we translated this approach to humans and compared the impact of E2 synthesis inhibition on memory performance and hippocampal activity in post-menopausal women taking letrozole (n = 21) to controls (n = 24). In particular, we employed various behavioral memory paradigms that allow the disentanglement of hippocampus-dependent and -independent memory. Consistent with the literature on rodents, E2 synthesis inhibition specifically impaired hippocampus-dependent memory, however, this did not apply to the same degree to all of the employed paradigms. On the neuronal level, E2 depletion tended to decrease hippocampal activity during encoding, whereas it increased activity in the anterior cingulate and the dorsolateral prefrontal cortex. We thus infer that the inhibition of E2 synthesis specifically impairs hippocampal functioning in humans, whereas the increased prefrontal activity presumably reflects a compensatory mechanism, which is already known from studies on cognitive aging and Alzheimer's disease.
[Mh] Termos MeSH primário: Estradiol/biossíntese
Hipocampo/efeitos dos fármacos
Memória/efeitos dos fármacos
Inibidores da Síntese de Esteroides/farmacologia
[Mh] Termos MeSH secundário: Idoso
Feminino
Giro do Cíngulo/efeitos dos fármacos
Seres Humanos
Potenciação de Longa Duração/efeitos dos fármacos
Estudos Longitudinais
Imagem por Ressonância Magnética
Memória de Curto Prazo/efeitos dos fármacos
Meia-Idade
Nitrilos/farmacologia
Pós-Menopausa
Córtex Pré-Frontal/efeitos dos fármacos
Desempenho Psicomotor/efeitos dos fármacos
Inquéritos e Questionários
Triazóis/farmacologia
Aprendizagem Verbal/efeitos dos fármacos
Testes de Associação de Palavras
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Nitriles); 0 (Steroid Synthesis Inhibitors); 0 (Triazoles); 2Z07MYW1AZ (anastrozole); 4TI98Z838E (Estradiol); 7LKK855W8I (letrozole)
[Em] Mês de entrada:1601
[Cu] Atualização por classe:150420
[Lr] Data última revisão:
150420
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150413
[St] Status:MEDLINE



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