RESUMO
OBJECTIVES: The aim of this study was to investigate the impact of intensively lowered low-density lipoprotein cholesterol (LDL-C) level on the deferred lesion prognosis after revascularization deferral based on fractional flow reserve (FFR). BACKGROUND: Lowering LDL-C is associated with lower cardiovascular event rate, but its benefit on the deferred lesion prognosis has not been well evaluated. METHODS: This retrospective, single-center, observational study analyzed 192 deferred lesions with FFR value >0.80 in 192 patients with stable coronary artery disease. According to the first follow-up LDL-C level, they were assigned to the LOW group (<70 mg/dL) or the HIGH group (≥70 mg/dL). Deferred lesion failure (DLF) was defined as the composite of deferred lesion revascularization and deferred vessel myocardial infarction. RESULTS: Of all participants, 61 and 131 patients were assigned to the LOW and the HIGH group, respectively. During the median follow-up of 2.8 years, DLF occurred in 1 and 14 patients in the LOW group and the HIGH group (1.6% and 10.7%, log-rank p = .043), respectively. The incidence of any unplanned revascularization was also significantly lower in the LOW group than in the HIGH group (3.3% vs. 14.5%, log-rank p = .032). CONCLUSIONS: The incidence of DLF was significantly lower in the patients with LDL-C < 70 mg/dL than in those with LDL-C ≥ 70 mg/dL at the first follow-up after FFR-based deferral of revascularization.
Assuntos
Anticolesterolemiantes/uso terapêutico , LDL-Colesterol/sangue , Doença da Artéria Coronariana/terapia , Estenose Coronária/terapia , Dislipidemias/tratamento farmacológico , Revascularização Miocárdica , Idoso , Anticolesterolemiantes/efeitos adversos , Biomarcadores/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/fisiopatologia , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/etiologia , Estenose Coronária/fisiopatologia , Progressão da Doença , Regulação para Baixo , Dislipidemias/sangue , Dislipidemias/complicações , Dislipidemias/diagnóstico , Ezetimiba/uso terapêutico , Feminino , Reserva Fracionada de Fluxo Miocárdico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Tempo para o Tratamento , Resultado do TratamentoRESUMO
A fluorescent aptamer sensor was applied to the analysis of extracellular chemical transmitter dynamics. We utilized a tocopherol-labeled aptamer, which allowed the direct anchoring of the fluorescent aptamer on the cell surface while retaining its performance as a fluorescent sensor. The fast-responsive fluorescent DNA aptamer sensor, which targets adenine compounds, was anchored on the surface of brain astrocytes. Fluorescence imaging of the aptamer-anchored astrocytes enabled the real-time monitoring of release of adenine compounds as a gliotransmitter, which was synchronized with calcium wave propagation in neighboring cells.
Assuntos
Adenina/análise , Aptâmeros de Nucleotídeos/química , Astrócitos/citologia , Técnicas Biossensoriais/métodos , Corantes Fluorescentes/química , Tocoferóis/química , Adenina/metabolismo , Animais , Astrócitos/metabolismo , Encéfalo/citologia , Sinalização do Cálcio , Células Cultivadas , Células HeLa , Humanos , Microscopia de Fluorescência/métodos , Modelos Moleculares , RatosRESUMO
BACKGROUND: Current expert consensus recommends remote monitoring for cardiac implantable electronic devices, with at least annual in-office follow-up. We studied safety and resource consumption of exclusive remote follow-up (RFU) in pacemaker patients for 2 years. METHODS: In Japan, consecutive pacemaker patients committed to remote monitoring were randomized to either RFU or conventional in-office follow-up (conventional follow-up) at twice yearly intervals. RFU patients were only seen if indicated by remote monitoring. All returned to hospital after 2 years. The primary end point was a composite of death, stroke, or cardiovascular events requiring surgery, and the primary hypothesis was noninferiority with 5% margin. RESULTS: Of 1274 randomized patients (50.4% female, age 77±10 years), 558 (RFU) and 550 (Conventional follow-up) patients reached either the primary end point or 24 months follow-up. The primary end point occurred in 10.9% and 11.8%, respectively (P=0.0012 for noninferiority). The median (interquartile range) number of in-office follow-ups was 0.50 (0.50-0.63) in RFU and 2.01 (1.93-2.05) in conventional follow-up per patient-year (P<0.001). Insurance claims for follow-ups and directly related diagnostic procedures were 18 800 Yen (16 500-20 700 Yen) in RFU and 21 400 Yen (16 700-25 900 Yen) in conventional follow-up (P<0.001). Only 1.4% of remote follow-ups triggered an unscheduled in-office follow-up, and only 1.5% of scheduled in-office follow-ups were considered actionable. CONCLUSIONS: Replacing periodic in-office follow-ups with remote follow-ups for 2 years in pacemaker patients committed to remote monitoring does not increase the occurrence of major cardiovascular events and reduces resource consumption. Registration: URL: https://clinicaltrials.gov; Unique identifier: NCT01523704.
Assuntos
Arritmias Cardíacas/terapia , Estimulação Cardíaca Artificial , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Visita a Consultório Médico , Marca-Passo Artificial , Tecnologia de Sensoriamento Remoto/instrumentação , Telemedicina/instrumentação , Potenciais de Ação , Idoso , Idoso de 80 Anos ou mais , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/mortalidade , Arritmias Cardíacas/fisiopatologia , Estimulação Cardíaca Artificial/efeitos adversos , Estimulação Cardíaca Artificial/mortalidade , Desenho de Equipamento , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Tempo , Resultado do TratamentoRESUMO
Deep vein thrombosis occasionally causes paradoxical embolism in patients with a patent foramen ovale (PFO). We report the case of a 42-year-old female who was hospitalized for stroke. Detailed investigations revealed the existence of a PFO, pulmonary embolism, and ovarian vein thrombosis extending to inferior vena cava. She had a uterine myoma to be operated on but no other thrombophilic disorders. Anticoagulation therapy with direct oral anticoagulant successfully reduced the thrombus and prevented the recurrence of paradoxical embolism.
RESUMO
Two reversible one-electron transfers are observed for an electrode device made from C60 and an artificial lipid (see schematic drawing). Cyclic voltammetric studies reveal that the redox couples are unchanged even after 50 cycles, thus indicating that the C60 radical monoanion and the C60 dianion generated in aqueous solution are very stable.
RESUMO
Using T-cell receptor (TCR) transgenic mice, we demonstrate that TCR stimulation of naive CD4(+) T cells induces transient T-bet expression, interleukin (IL)-12 receptor beta2 up-regulation, and GATA-3 down-regulation, which leads to T helper (Th)1 differentiation even when the cells are stimulated with peptide-loaded I-A(b)-transfected Chinese hamster ovary cells in the absence of interferon-gamma (IFN-gamma) and IL-12. Sustained IFN-gamma and IL-12 stimulation augments naive T-cell differentiation into Th1 cells. Intriguingly, a significant Th1 response is observed even when T-bet(-/-) naive CD4(+) T cells are stimulated through TCR in the absence of IFN-gamma or IL-12. Stimulation of naive CD4(+) T cells in the absence of IFN-gamma or IL-12 with altered peptide ligand, whose avidity to the TCR is lower than that of original peptide, fails to up-regulate transient T-bet expression, sustains GATA-3 expression, and induces differentiation into Th2 cells. These results support the notion that direct interaction between TCR and peptide-loaded antigen-presenting cells, even in the absence of T-bet expression and costimulatory signals, primarily determine the fate of naive CD4(+) T cells to Th1 cells.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Proteínas com Domínio T/metabolismo , Animais , Células Apresentadoras de Antígenos/imunologia , Células CHO , Diferenciação Celular/imunologia , Proliferação de Células , Células Cultivadas , Cricetinae , Cricetulus , Interferon gama/imunologia , Interleucina-12/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Fragmentos de Peptídeos/imunologia , Reação em Cadeia da Polimerase/métodos , Transdução de Sinais/imunologia , Baço/imunologia , Células Th1/imunologiaAssuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Furanos/administração & dosagem , Furanos/farmacologia , Cetonas/administração & dosagem , Cetonas/farmacologia , Moduladores de Tubulina/administração & dosagem , Moduladores de Tubulina/farmacologia , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Neoplasias da Mama/patologia , Ensaios Clínicos como Assunto , Esquema de Medicação , Aprovação de Drogas , Descoberta de Drogas , Feminino , Furanos/efeitos adversos , Furanos/farmacocinética , Humanos , Infusões Intravenosas , Cetonas/efeitos adversos , Cetonas/farmacocinética , Metástase Neoplásica , Resultado do Tratamento , Moduladores de Tubulina/efeitos adversos , Moduladores de Tubulina/farmacocinéticaAssuntos
Doenças Assintomáticas , Eletrocardiografia Ambulatorial/métodos , Hipertireoidismo/diagnóstico , Cardiomiopatia de Takotsubo/diagnóstico , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipertireoidismo/complicações , Hipertireoidismo/fisiopatologia , Cardiomiopatia de Takotsubo/etiologia , Cardiomiopatia de Takotsubo/fisiopatologiaRESUMO
The effector CD8(+) T cells recognize major histocompatibility complex (MHC) class I binding altered self-peptides expressed in tumour cells. Although the requirement for CD4(+) T helper type 1 (Th1) cells in regulating CD8(+) T cells has been documented, their target epitopes and functional impact in antitumour responses remain unclear. We examined whether a potent immunogenic peptide of Mycobacterium tuberculosis eliciting Th1 immunity contributes to the generation of CD8(+) T cells and to protective antitumour immune responses to unrelated tumour-specific antigens. Peptide-25, a major Th epitope of Ag85B from M. tuberculosis preferentially induced CD4(+) Th1 cells in C57BL/6 mice and had an augmenting effect on Th1 generation for coimmunized unrelated antigenic peptides. Coimmunization of mice with Peptide-25 and ovalbumin (OVA) or Peptide-25 and B16 melanoma peptide [tyrosinase-related protein-2 (TRP-2)] for MHC class I led to a profound increase in CD8(+) T cells specific for OVA and TRP-2 peptides, respectively. This heightened response depended on Peptide-25-specific CD4(+) T cells and interferon-gamma-producing T cells. In tumour protection assays, immunization with Peptide-25 and OVA resulted in the enhancement of CD8(+) cytotoxic cell generation specific for OVA and the growth inhibition of EL-4 thymoma expressing OVA peptide leading to the tumour rejection. These phenomena were not achieved by immunization with OVA alone. Peptide-25-reactive Th1 cells counteractivated dendritic cells in the presence of Peptide-25 leading them to activate and present OVA peptide to CD8(+) cytotoxic T cells.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Timoma/terapia , Neoplasias do Timo/terapia , Aciltransferases/imunologia , Animais , Apresentação de Antígeno/imunologia , Antígenos de Bactérias/imunologia , Células Cultivadas , Citotoxicidade Imunológica/imunologia , Células Dendríticas/imunologia , Epitopos de Linfócito T/imunologia , Imunização , Interferon gama/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Transplante de Neoplasias , Ovalbumina/imunologia , Timoma/imunologia , Neoplasias do Timo/imunologiaRESUMO
CD4+ Th1 cells play a critical role in the induction of cell-mediated immune responses that are important for the eradication of intracellular pathogens. Peptide-25 is the major Th1 epitope for Ag85B of Mycobacterium tuberculosis and is immunogenic in I-Ab mice. To elucidate the role of the TCR and IFN-gamma/IL-12 signals in Th1 induction, we generated TCR transgenic mice (P25 TCR-Tg) expressing TCR alpha- and beta-chains of Peptide-25-reactive cloned T cells and analyzed Th1 development of CD4+ T cells from P25 TCR-Tg. Naive CD4+ T cells from P25 TCR-Tg differentiate into both Th1 and Th2 cells upon stimulation with anti-CD3. Naive CD4+ T cells from P25 TCR-Tg preferentially develop Th1 cells upon Peptide-25 stimulation in the presence of I-Ab splenic antigen-presenting cells under neutral conditions. In contrast, a mutant of Peptide-25 can induce solely Th2 differentiation. Peptide-25-induced Th1 differentiation is observed even in the presence of anti-IFN-gamma and anti-IL-12. Furthermore, naive CD4+ T cells from STAT1 deficient P25 TCR-Tg also differentiate into Th1 cells upon Peptide-25 stimulation. Moreover, Peptide-25-loaded I-Ab-transfected Chinese hamster ovary cells induce Th1 differentiation of naive CD4+ T cells from P25 TCR-Tg in the absence of IFN-gamma or IL-12. These results imply that interaction between Peptide-25/I-Ab and TCR may primarily influence determination of the fate of naive CD4+ T cells in their differentiation towards the Th1 subset.