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1.
Case Rep Oncol ; 14(3): 1447-1453, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899235

RESUMO

A 77-year-old woman with postoperative recurrent non-small cell lung adenocarcinoma, which exhibited an epidermal growth factor receptor (EGFR) L858R mutation, was treated with gefitinib and erlotinib. Seven years after the start of treatment, the patient experienced a recurrence of malignant pleural effusion. However, 3 different genetic tests revealed that the lung adenocarcinoma cells in the pleural effusion had lost EGFR L858R mutation, suggesting that long-term treatment with EGFR-tyrosine kinase inhibitors (TKIs) converted EGFR mutation from positive to negative. The negative conversion of EGFR mutation as a mechanism of acquired resistance to EGFR-TKIs is considered rare and needs to be further investigated.

2.
Stem Cell Res Ther ; 12(1): 506, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34530920

RESUMO

BACKGROUND: Mesenchymal stromal cells (MSCs) are a potential therapeutic tool for pulmonary fibrosis. However, ex vivo MSC expansion using serum poses risks of harmful immune responses or unknown pathogen infections in the recipients. Therefore, MSCs cultured in serum-free media (SF-MSCs) are ideal for clinical settings; however, their efficacy in pulmonary fibrosis is unknown. Here, we investigated the effects of SF-MSCs on bleomycin-induced pulmonary inflammation and fibrosis compared to those of MSCs cultured in serum-containing media (S-MSCs). METHODS: SF-MSCs and S-MSCs were characterized in vitro using RNA sequence analysis. The in vivo kinetics and efficacy of SF-MSC therapy were investigated using a murine model of bleomycin-induced pulmonary fibrosis. For normally distributed data, Student's t test and one-way repeated measures analysis of variance followed by post hoc Tukey's test were used for comparison between two groups and multiple groups, respectively. For non-normally distributed data, Kruskal-Wallis and Mann-Whitney U tests were used for comparison between groups, using e Bonferroni's correction for multiple comparisons. All tests were two-sided, and P < 0.05 was considered statistically significant. RESULTS: Serum-free media promoted human bone marrow-derived MSC expansion and improved lung engraftment of intravenously administered MSCs in recipient mice. SF-MSCs inhibited the reduction in serum transforming growth factor-ß1 and the increase of interleukin-6 in both the serum and the bronchoalveolar lavage fluid during bleomycin-induced pulmonary fibrosis. SF-MSC administration increased the numbers of regulatory T cells (Tregs) in the blood and lungs more strongly than in S-MSC administration. Furthermore, SF-MSCs demonstrated enhanced antifibrotic effects on bleomycin-induced pulmonary fibrosis, which were diminished by antibody-mediated Treg depletion. CONCLUSIONS: SF-MSCs significantly suppressed BLM-induced pulmonary inflammation and fibrosis through enhanced induction of Tregs into the lungs and corrected the dysregulated cytokine balance. Therefore, SF-MSCs could be a useful tool for preventing pulmonary fibrosis progression without the demerits of serum use.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Fibrose Pulmonar , Animais , Bleomicina/toxicidade , Medula Óssea , Células Cultivadas , Meios de Cultura Livres de Soro , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/terapia , Linfócitos T Reguladores
3.
Stem Cell Res Ther ; 12(1): 471, 2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34425896

RESUMO

BACKGROUND: Aldehyde dehydrogenase (ALDH) is highly expressed in stem/progenitor cells in various tissues, and cell populations with high ALDH activity (ALDHbr) are associated with tissue repair. However, little is known about lung-resident ALDHbr. This study was performed to clarify the characteristics of lung-resident ALDHbr cells and to evaluate their possible use as a tool for cell therapy using a mouse model of bleomycin-induced pulmonary fibrosis. METHODS: The characteristics of lung-resident/nonhematopoietic (CD45-) ALDHbr cells were assessed in control C57BL/6 mice. The kinetics and the potential usage of CD45-/ALDHbr for cell therapy were investigated in bleomycin-induced pulmonary fibrosis. Localization of transferred CD45-/ALDHbr cells was determined using mCherry-expressing mice as donors. The effects of aging on ALDH expression were also assessed using aged mice. RESULTS: Lung CD45-/ALDHbr showed higher proliferative and colony-forming potential than cell populations with low ALDH activity. The CD45-/ALDHbr cell population, and especially its CD45-/ALDHbr/PDGFRα+ subpopulation, was significantly reduced in the lung during bleomycin-induced pulmonary fibrosis. Furthermore, mRNA expression of ALDH isoforms was significantly reduced in the fibrotic lung. When transferred in vivo into bleomycin-pretreated mice, CD45-/ALDHbr cells reached the site of injury, ameliorated pulmonary fibrosis, recovered the reduced expression of ALDH mRNA, and prolonged survival, which was associated with the upregulation of the retinol-metabolizing pathway and the suppression of profibrotic cytokines. The reduction in CD45-/ALDHbr/PDGFRα+ population was more remarkable in aged mice than in young mice. CONCLUSIONS: Our results strongly suggest that the lung expression of ALDH and lung-resident CD45-/ALDHbr cells are involved in pulmonary fibrosis. The current study signified the possibility that CD45-/ALDHbr cells could find application as novel and useful cell therapy tools in pulmonary fibrosis treatment.


Assuntos
Fibrose Pulmonar , Células-Tronco , Aldeído Desidrogenase , Animais , Bleomicina/toxicidade , Pulmão , Camundongos , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/terapia
4.
Gan To Kagaku Ryoho ; 48(4): 523-525, 2021 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-33976038

RESUMO

We present the case of a 72‒year‒old male patient with anorexia who was diagnosed with advanced gastric cancer with multiple liver metastasis. He had marked hypoglycemia and lightheadedness from the time of admission. The serum insulin level was very low and other endocrinology test results were normal. He was finally diagnosed with non‒islet cell tumor hypoglycemia(NICTH)based on IHC findings that tumor cells expressed insulin‒like growth factor (IGF)Ⅱ. After the patient received intravenous glucocorticoid therapy along with S‒1 plus CDDP combination chemotherapy, the hypoglycemia was quickly resolved. However, he developed septic shock in reaction to the chemotherapy and died on the 35th day of hospitalization. The autopsy showed the presence of IGF‒Ⅱ in the liver metastasis, as well as in the primary tumor.


Assuntos
Hipoglicemia , Neoplasias Hepáticas , Neoplasias Gástricas , Idoso , Autopsia , Humanos , Hipoglicemia/etiologia , Fator de Crescimento Insulin-Like II , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Neoplasias Gástricas/complicações , Neoplasias Gástricas/tratamento farmacológico
5.
Respir Investig ; 58(6): 465-472, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32762953

RESUMO

BACKGROUND: Several prognostic factors for pleuroparenchymal fibroelastosis (PPFE) have recently been reported. However, detailed high-resolution computed tomography (HRCT) findings have not yet been evaluated as prognostic factors. This study retrospectively investigated whether HRCT findings are prognostic factors in patients with PPFE compared to those with idiopathic pulmonary fibrosis (IPF). METHODS: Patients with PPFE and IPF diagnosed at our hospital between January 2008 and December 2016 were enrolled. Clinical and HRCT characteristics were obtained. In addition to our patients, we also analyzed data of PPFE patients whose cause of death had been identified in previous studies. RESULTS: We enrolled 15 patients with PPFE and 75 patients with IPF. Consolidation and maximum pleural thickening were significantly higher in patients with PPFE than in those with IPF (both P < .001). Fibrosis score, honeycomb area, and traction bronchiectasis were not significantly different between these patient groups but were significant prognostic factors in patients with PPFE in univariate analysis (P = .021, P = .017, and P = .014, respectively). The proportions of deaths by acute exacerbation or lung cancer were significantly lower in patients with PPFE than in those with IPF (P < .001 and P = .001, respectively), whereas death by respiratory failure was significantly more frequent in PPFE patients (P < .001). CONCLUSIONS: HRCT findings, such as fibrosis score, honeycomb area, and traction bronchiectasis, were independent prognostic factors in patients with PPFE. Respiratory failure, but not acute exacerbation and lung cancer, was the main cause of death in patients with PPFE.


Assuntos
Fibrose Pulmonar Idiopática , Doenças Pleurais , Humanos , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
6.
Beilstein J Org Chem ; 15: 863-873, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31019579

RESUMO

Novel caged nitroxides (nitroxide donors) with near-infrared two-photon (TP) responsive character, 2,2,6,6-tetramethyl-1-(1-(2-(4-nitrophenyl)benzofuran-6-yl)ethoxy)piperidine (2a) and its regioisomer 2b, were designed and synthesized. The one-photon (OP) (365 ± 10 nm) and TP (710-760 nm) triggered release (i.e., uncaging) of the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical under air atmosphere were discovered. The quantum yields for the release of the TEMPO radical were 2.5% (2a) and 0.8% (2b) in benzene at ≈1% conversion of 2, and 13.1% (2a) and 12.8% (2b) in DMSO at ≈1% conversion of 2. The TP uncaging efficiencies were determined to be 1.1 GM at 740 nm for 2a and 0.22 GM at 730 nm for 2b in benzene. The cytocidal effect of compound 2a on lung cancer cells under photolysis conditions was also assessed to test the efficacy as anticancer agents. In a medium containing 100 µg mL-1 of 2a exposed to light, the number of living cells decreased significantly compared to the unexposed counterparts (65.8% vs 85.5%).

7.
J Cell Mol Med ; 23(4): 2984-2994, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30734495

RESUMO

Plasminogen activator inhibitor-1 (PAI-1) promotes pulmonary fibrosis through increasing myofibroblast (MF) characteristics, expressing alpha-smooth muscle actin (α-SMA) in fibroblasts. Fibroblasts in the tumour stroma are called cancer-associated fibroblasts (CAFs). Some CAFs have MF characteristics and substantially promote tumour progression and chemotherapy resistance. This study determined whether inhibition of PAI-1 suppressed MF characteristics of CAFs and limited chemotherapy resistance in lung cancer. To investigate cellular PAI-1 expression and its correlation with α-SMA expression of CAFs, 34 patients' paraffin-embedded lung adenocarcinoma tissue sections were immunohistochemically stained for PAI-1 and α-SMA. Immunohistochemical analysis of lung adenocarcinoma tissues showed that PAI-1 expression was correlated with that of α-SMA (r = 0.71, p < 0.001). Furthermore, in vitro, α-SMA expression of CAFs was limited by PAI-1 inhibition, and apoptosis of CAFs was increased. In addition, the effectiveness of cisplatin on lung cancer cells co-cultured with CAFs was increased by suppressing α-SMA expression using PAI-1 inhibitor. In lung adenocarcinoma tissues, PAI-1 expression was associated with T factor and TNM stage. Our data suggest that inhibition of PAI-1 increased the chemotherapeutic effect on lung cancer through suppressing the MF characteristics of CAFs. Hence, PAI-1 might be a promising therapeutic target for patients with chemotherapeutic-resistant lung cancer with CAFs.


Assuntos
Antineoplásicos/farmacologia , Biomarcadores Tumorais/análise , Fibroblastos Associados a Câncer/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/tratamento farmacológico , Miofibroblastos/efeitos dos fármacos , Inibidor 1 de Ativador de Plasminogênio/química , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Ciclo Celular , Proliferação de Células , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Prognóstico , Estudos Retrospectivos , Células Tumorais Cultivadas
8.
Cancer Lett ; 442: 31-39, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30389434

RESUMO

Polymorphic epithelial mucin (MUC1) is generally overexpressed on the surface of most adenocarcinomas including breast cancer. MUC1 is associated with chemotherapeutic resistance and immune evasion of cancer cells; however, the association between MUC1 and trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) remains unclear. In this study, using six breast cancer cell lines with differing expression levels and MUC1 distribution, the present results show that cells with MUC1 overexpression and uniform surface distribution were resistant to trastuzumab-mediated ADCC. Importantly, trastuzumab resistance was reversed upon siRNA-mediated MUC1 knockdown and by using anti-KL-6/MUC1 monoclonal antibody (mAb). Additionally, we visually confirmed that anti-KL-6/MUC1 mAb induced capping of MUC1 molecules on the cell surface, resulting the in death of these cells. These results suggest that not only the quantity but also the cell-surface distribution of MUC1 affects the sensitivity of breast cancer cells to trastuzumab-mediated ADCC.


Assuntos
Anticorpos Monoclonais/farmacologia , Citotoxicidade Celular Dependente de Anticorpos/efeitos dos fármacos , Antineoplásicos Imunológicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Mucina-1/metabolismo , Trastuzumab/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Humanos , Mucina-1/imunologia , Transdução de Sinais/efeitos dos fármacos
9.
Intern Med ; 56(24): 3327-3331, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-29021448

RESUMO

Recently, sirolimus, an inhibitor of mammalian target of rapamycin, was reported to decrease chylous effusion in patients with lymphangioleimyomatosis (LAM). We herein report a case of a 34-year-old woman with LAM who developed refractory chylothorax and chylous ascites during sirolimus therapy. In this case, to reduce chylous effusion, we administered octreotide, which is often used to control postoperative chylous effusion, in addition to the sirolimus therapy. This combination therapy reduced the chylothorax and chylous ascites. For patients with LAM, octreotide therapy in addition to sirolimus may be effective for treating sirolimus-refractory chylous effusion.


Assuntos
Ascite Quilosa/complicações , Ascite Quilosa/tratamento farmacológico , Imunossupressores/uso terapêutico , Linfangioleiomiomatose/complicações , Octreotida/uso terapêutico , Sirolimo/uso terapêutico , Adulto , Quilotórax/complicações , Quilotórax/tratamento farmacológico , Resistência a Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/administração & dosagem , Octreotida/administração & dosagem , Sirolimo/administração & dosagem
10.
Coron Artery Dis ; 20(4): 260-6, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19424058

RESUMO

BACKGROUND: Pathological studies report that acute ST segment elevation myocardial infarction (STEMI) is caused not only by plaque rupture but also by other causes, such as erosion. To test our hypothesis that different lesion morphologies result in different clinical outcomes, we used intravascular ultrasound (IVUS) to investigate the relationship between lesion morphology and infarct size after successful primary angioplasty. METHODS: Our 72 consecutive first anterior STEMI patients underwent preintervention IVUS and were successfully recanalized with primary angioplasty. Using echocardiography, we analyzed left-ventricular wall motion to obtain a Wall Motion Score Index (WMSI) before angioplasty and 1 month after the onset, and used thallium myocardial scintigraphy 1 month after the onset to obtain computer-generated severity scores. Patients were divided into a rupture group (n = 30) and a nonrupture group (n = 42) on the basis of preintervention IVUS findings. RESULTS: Peak creatine kinase levels (3150+/-357 vs. 2256+/-238 IU/l, P = 0.03) and severity score (758+/-114 vs. 474+/-75, P = 0.03) in the rupture group were significantly higher. Despite there being no difference in baseline WMSI (1.55+/-0.04 vs. 1.58+/-0.03, P = 0.45), improvement in WMSI in the rupture group was significantly less pronounced (0.08+/-0.02 vs. 0.18+/-0.03, P = 0.01). CONCLUSION: STEMI caused by plaque rupture is associated with a large degree of myocardial damage and poor functional recovery as compared with STEMI of different etiologies, even after successful primary angioplasty. Our results suggest that lesion morphology may affect clinical outcomes.


Assuntos
Angioplastia Coronária com Balão , Doença da Artéria Coronariana/complicações , Infarto do Miocárdio/terapia , Miocárdio/patologia , Idoso , Biomarcadores/sangue , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/terapia , Creatina Quinase/sangue , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Contração Miocárdica , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Imagem de Perfusão do Miocárdio , Miocárdio/enzimologia , Estudos Prospectivos , Recuperação de Função Fisiológica , Ruptura , Índice de Gravidade de Doença , Radioisótopos de Tálio , Tomografia Computadorizada de Emissão de Fóton Único , Resultado do Tratamento , Ultrassonografia de Intervenção , Função Ventricular Esquerda
11.
Eur Heart J ; 29(1): 38-44, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17989077

RESUMO

AIMS: In this study, we investigated the relationship between longitudinal morphology reconstructed from pre-intervention intravascular ultrasound (IVUS) images and thrombolysis in myocardial infarction (TIMI) flow grade at initial angiograms in the acute phase of acute coronary syndrome (ACS). METHODS AND RESULTS: Our patient population comprised 72 ACS patients in whom we obtained successful reconstructed longitudinal images. On the basis of the site of the maximum aperture of rupture in the longitudinally reconstructed IVUS images, patients were divided into three groups: plaques with rupture in the proximal shoulder (proximal type; n = 28), mid-portion (mid-type; n = 18), and distal shoulder (distal type; n = 26) of the plaque. There were no differences in terms of coronary risk factors or the angiographic findings. The proximal-type group more frequently showed TIMI 0 on initial angiogram (proximal type, 86%; mid-type, 50%; and distal type, 31%; P = 0.002). A multivariable logistic regression model revealed that the presence of a proximal-type rupture correlated with the presentation of ST-elevation myocardial infarction (P = 0.019; odds ratio, 8.12; 95% CI, 1.404-49.996). CONCLUSIONS: Longitudinal morphological features in a ruptured plaque may affect the formation of obstructive thrombus in ACS. Our results suggest that longitudinal morphology may be an important determinant of coronary artery occlusion.


Assuntos
Síndrome Coronariana Aguda/diagnóstico por imagem , Trombose Coronária/diagnóstico por imagem , Infarto do Miocárdio/diagnóstico por imagem , Síndrome Coronariana Aguda/metabolismo , Síndrome Coronariana Aguda/patologia , Adulto , Idoso , Angiografia Coronária/métodos , Trombose Coronária/metabolismo , Trombose Coronária/patologia , Ecocardiografia Tridimensional/métodos , Ruptura Cardíaca Pós-Infarto/diagnóstico por imagem , Ruptura Cardíaca Pós-Infarto/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/patologia
13.
Pacing Clin Electrophysiol ; 28(6): 549-54, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15955188

RESUMO

BACKGROUND: Although many studies on Brugada syndrome have been done, with many reports of genetic findings and clinical features, little evidence exists to support the role of this syndrome in sudden cardiac death in a juvenile population. We sought to determine the prevalence and clinical course in children exhibiting Brugada-type ECG in a community-based population. METHODS: Our study population comprised 21,944 subjects (11,282 boys and 10,662 girls) who underwent ECG during their first-year elementary school health examinations between 1992 and 2001 in Izumi City, Osaka. Brugada-type ECG was defined as demonstrating ST-segment elevation (coved or saddle-back type, J wave amplitude > or =0.2 mV) in the right precordial leads. We also divided Brugada-type ECGs into three types according to a consensus report. Type 1: coved ST-segment elevation displaying high J wave amplitude followed by a negative T wave; Type 2: high take-off and gradually descending ST-segment elevation (remaining > or =1 mm) followed by a positive or biphasic T wave; and Type 3: ST-segment elevation of <1 mm of both types. RESULTS: Four subjects showed Brugada-type ECG (0.02%) (2 boys and 2 girls). Only one subject, a girl, met Type 1 criteria (0.005%). No history of structural heart disease was documented in these four subjects. During 6.8 +/- 1.0 years of follow-up, no episode of unexpected sudden death, syncopal attack, and fatal arrhythmia occurred. CONCLUSIONS: The prevalence of Brugada-type ECG in a juvenile population was extremely low. To investigate when the typical Brugada-type ECG might be manifested, it could be necessary to check ECGs after adolescence.


Assuntos
Bloqueio de Ramo/etnologia , Eletrocardiografia , Bloqueio de Ramo/fisiopatologia , Criança , Morte Súbita Cardíaca , Feminino , Humanos , Japão , Masculino , Prevalência , Síndrome
14.
J Am Coll Cardiol ; 45(10): 1594-9, 2005 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-15893172

RESUMO

OBJECTIVES: This study sought to investigate the relationship between multiple plaque ruptures, C-reactive protein (CRP), and clinical prognosis in acute myocardial infarction (AMI). BACKGROUND: Several studies have demonstrated that ruptured or vulnerable plaques exist not only at the culprit lesion but also in the whole coronary artery in some acute coronary syndrome (ACS) patients. Recent studies have reported that a ruptured plaque at the culprit lesion is associated with elevated CRP, which indicates a poor prognosis in patients with ACS. METHODS: We performed intravascular ultrasound in 45 infarct-related arteries and another 84 major coronary arteries in 45 first AMI patients. RESULTS: Plaque rupture was observed in 21 patients (47%) at the culprit site. Intravascular ultrasound revealed 17 additional plaque ruptures at remote sites in 11 patients (24%). Patients with multiple risk factors were more frequently found in our multiple-plaque rupture patients compared with single-plaque rupture or nonrupture patients (82% vs. 40% vs. 29%, p = 0.01). High-sensitive CRP levels had a positive correlation with the number of plaque ruptures (p < 0.01). All culprit lesions were successfully treated by percutaneous coronary intervention. Patients with multiple plaque rupture showed significantly poor prognosis compared with others (p = 0.01). CONCLUSIONS: Multiple plaque rupture is associated with systemic inflammation, and patients with multiple plaque rupture can be expected to show a poor prognosis. Our results suggest that AMI treatment should focus not only on stabilization of the culprit site but also a systemic approach to systemic stabilization of the arteries.


Assuntos
Proteína C-Reativa/metabolismo , Doença da Artéria Coronariana/imunologia , Trombose Coronária/imunologia , Infarto do Miocárdio/imunologia , Idoso , Angioplastia Coronária com Balão , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Trombose Coronária/diagnóstico por imagem , Trombose Coronária/terapia , Vasos Coronários/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/terapia , Prognóstico , Fatores de Risco , Ruptura Espontânea , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico por imagem , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Síndrome de Resposta Inflamatória Sistêmica/terapia , Ultrassonografia
16.
Am J Cardiol ; 92(10): 1208-11, 2003 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-14609600

RESUMO

We investigated the correlation between lesion morphology with preintervention intravascular ultrasound and in-stent restenosis in 72 patients with acute myocardial infarction (AMI). Multivariate logistic regression analysis showed that the presence of ruptured plaque was the only predictive factor of in-stent restenosis after primary stenting for AMI.


Assuntos
Implante de Prótese Vascular/efeitos adversos , Oclusão de Enxerto Vascular/etiologia , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/cirurgia , Stents/efeitos adversos , Ultrassonografia de Intervenção , Idoso , Angiografia Coronária , Feminino , Oclusão de Enxerto Vascular/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Cuidados Pré-Operatórios
17.
Circulation ; 108(3): 282-5, 2003 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-12835218

RESUMO

BACKGROUND: Elevated serum C-reactive protein (CRP) is of clinical significance in the management of acute coronary syndromes, but there have been few in vivo studies detailing the relation between lesion morphology and elevated CRP in the setting of acute myocardial infarction (AMI). In this study, we investigated the relation between lesion morphology as seen under preintervention intravascular ultrasound (IVUS) and CRP in the acute phase of AMI. METHODS AND RESULTS: Our patient population comprised 90 consecutive patients with AMI who underwent preintervention IVUS within 6 hours of the onset of symptoms. Patients were divided into an elevated CRP group (> or =3 mg/L) or a normal CRP group on the basis of serum CRP levels. There were no differences in patient characteristics or angiographic findings. We observed significantly more plaque rupture in the elevated CRP group than in the normal CRP group (70% versus 43%, P=0.01). A multivariate logistic regression model revealed that the presence of ruptured plaque alone correlated with elevation of serum CRP (P=0.02; odds ratio, 3.35; 95% CI, 1.22 to 9.18). CONCLUSIONS: Elevated CRP may be related to the presence of ruptured plaque. Our results suggest that in the setting of AMI, elevated CRP levels may reflect the inflammatory activity of a ruptured plaque.


Assuntos
Proteína C-Reativa/análise , Doença da Artéria Coronariana/sangue , Infarto do Miocárdio/sangue , Biomarcadores/sangue , Angiografia Coronária , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Vasos Coronários/diagnóstico por imagem , Creatina Quinase/sangue , Creatina Quinase Forma MB , Progressão da Doença , Feminino , Humanos , Isoenzimas/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico , Razão de Chances , Valor Preditivo dos Testes , Ruptura Espontânea/diagnóstico por imagem , Troponina T/sangue , Ultrassonografia de Intervenção
18.
Hypertens Res ; 25(3): 461-6, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-12135327

RESUMO

The mechanism and treatment of hypertensive systolic heart failure are not well defined. We compared the effect of an angiotensin-converting enzyme inhibitor (cilazapril, 10 mg/kg), an angiotensin receptor blocker (candesartan, 3 mg/kg), a calcium channel blocker (benidipine, 1, 3 or 6 mg/kg), and the same calcium channel blocker combined with renin-angiotensin blockers on systolic heart failure in Dahl salt-sensitive (DS) rats. DS rats were fed an 8% Na diet from 6 weeks of age and then subjected to the above drug treatments. Benidipine (1 mg/kg), cilazapril, and candesartan had compatible hypotensive effects and similar beneficial effects on cardiac hypertrophy, gene expression, and survival rate. The combination of benidipine with cilazapril or candesartan was found to have no additional beneficial effects on the above parameters, with the exception of a reduction in atrial natriuretic polypeptide gene expression. On the other hand, candesartan normalized serum creatinine, but serum creatinine was unaffected by either benidipine at 1 or 3 mg/kg or cilazapril. Further, the combined use of benidipine and either candesartan or cilazapril resulted in an additional reduction of urinary albumin excretion in DS rats. Thus systolic heart failure in DS rats is mainly mediated by hypertension, while renal dysfunction of DS rats is due to both hypertension and the AT1 receptor itself. These findings suggest that the combination of a calcium channel blocker with an AT1 receptor blocker or ACE inhibitor may be more effective in treating the renal dysfunction associated with systolic heart failure than monotherapy with either agent alone. However, further studies will be needed before reaching any definitive conclusion on the efficacy of this combination therapy in patients with heart failure.


Assuntos
Antagonistas de Receptores de Angiotensina , Bloqueadores dos Canais de Cálcio/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Hipertensão/tratamento farmacológico , Sístole/fisiologia , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Animais , Fator Natriurético Atrial/genética , Pressão Sanguínea/efeitos dos fármacos , Cilazapril/administração & dosagem , Di-Hidropiridinas/administração & dosagem , Quimioterapia Combinada , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/mortalidade , Rim/efeitos dos fármacos , Peptídeo Natriurético Encefálico/genética , Tamanho do Órgão/efeitos dos fármacos , RNA Mensageiro/análise , Ratos , Receptor Tipo 1 de Angiotensina , Taxa de Sobrevida , Fator de Crescimento Transformador beta/genética
19.
Arterioscler Thromb Vasc Biol ; 22(1): 82-8, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11788465

RESUMO

Although platelet-derived growth factor (PDGF)-BB is thought to participate in vascular disorders, the mechanism of PDGF-induced vascular smooth muscle cell (SMC) proliferation is not fully understood. This study was undertaken to examine the role of c-Jun in PDGF-BB-induced proliferation of rat aortic SMCs. PDGF-BB (10 ng/mL) significantly increased activator protein (AP)-1 DNA binding activity in SMCs, followed by the increase in [(3)H]thymidine incorporation and cell number. SMCs were infected with recombinant adenovirus containing TAM67, a dominant-negative c-Jun lacking the transactivation domain of wild c-Jun (Ad-DN-c-Jun), to inhibit endogenous AP-1. Ad-DN-c-Jun, which specifically blocked AP-1 transcriptional activity, significantly inhibited PDGF-BB-induced increases in [(3)H]thymidine incorporation or cell number. As shown by flow cytometric analysis, Ad-DN-c-Jun inhibited PDGF-BB-induced entrance of SMCs into S phase, leading to a G(1) arrest. Ad-DN-c-Jun attenuated PDGF-BB-induced downregulation of p27(Kip1), as shown by Western blot analysis, and the prevented PDGF-BB-induced decrease in cyclin E/cyclin-dependent kinase 2 complex-associated p27(Kip1), as shown by immunoprecipitation study. Furthermore, protein kinase assay showed that Ad-DN-c-Jun blocked PDGF-BB-induced activation of cyclin-dependent kinase 2. Our results provide the first evidence that dominant-negative c-Jun inhibits PDGF-BB-induced vascular SMC proliferation by preventing the downregulation of p27(Kip1), thereby supporting the important role of c-Jun in vascular SMC proliferation.


Assuntos
Músculo Liso Vascular/citologia , Fator de Crescimento Derivado de Plaquetas/metabolismo , Proteínas Proto-Oncogênicas c-jun/fisiologia , Fator de Transcrição AP-1/metabolismo , Animais , Becaplermina , Proteínas de Ciclo Celular/metabolismo , Divisão Celular , Fase G1 , Masculino , Músculo Liso Vascular/metabolismo , Mutação , Proteínas Proto-Oncogênicas c-jun/genética , Proteínas Proto-Oncogênicas c-sis , Ratos , Ratos Sprague-Dawley , Receptores do Fator de Crescimento Derivado de Plaquetas/metabolismo
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