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1.
J Med Invest ; 71(1.2): 174-176, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38735716

RESUMO

BACKGROUND: Augmented reality navigation is the one of the navigation technologies that allows computer-generated virtual images to be projected onto a real-world environment. Augmented reality navigation can be used in spinal tumor surgery. However, it is unknown if there are any pitfalls when using this technique. CASE PRESENTATION: The patient in this report underwent complete resection of a cauda equina tumor at the L2-L3 level using microscope-based augmented reality navigation. Although the registration error of navigation was <1 mm, we found a discrepancy between the augmented reality navigation images and the actual location of the tumor, which we have called "navigation mismatch". This mismatch, which was caused by the mobility of the spinal tumor in the dura mater, seems to be one of the pitfalls of augmented reality navigation for spinal tumors. CONCLUSIONS: Combined use of intraoperative ultrasound and augmented reality navigation seems advisable in such cases. J. Med. Invest. 71 : 174-176, February, 2024.


Assuntos
Realidade Aumentada , Cauda Equina , Humanos , Cauda Equina/diagnóstico por imagem , Cauda Equina/cirurgia , Neoplasias do Sistema Nervoso Periférico/cirurgia , Neoplasias do Sistema Nervoso Periférico/diagnóstico por imagem , Cirurgia Assistida por Computador/métodos
2.
J Med Invest ; 71(1.2): 179-183, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38735718

RESUMO

Osteoporotic vertebral fracture (OVF) is common in the elderly population. In this report, we describe a case with radiculopathy due to foraminal stenosis caused by OVF in a very elderly patient that was treated successfully by full-endoscopic foraminotomy under local anesthesia. The patient was an 89-year-old woman who presented with a chief complaint of left leg pain for 5 years. She visited a couple of hospitals and finally consulted us to determine the exact cause of the pain. Computed tomography scans were obtained and selective nerve root block at L3 was performed. The diagnosis was radiculopathy at L3 due to foraminal stenosis following OVF. The patient had severe heart disease, so we decided to avoid surgery under general anesthesia and planned full-endoscopic spine surgery under local anesthesia. We performed transforaminal full-endoscopic lumbar foraminotomy at L3-L4 to decompress the L3 nerve root. The leg pain disappeared completely immediately after surgery. Postoperative computed tomography confirmed appropriate bone resection. The leg pain did not recur during a year of postoperative follow-up. OVF may cause lumbar radiculopathy as a result of foraminal stenosis, and transforaminal full-endoscopic lumbar foraminotomy under local anesthesia would be the best option in an elderly patient with poor general condition. J. Med. Invest. 71 : 179-183, February, 2024.


Assuntos
Anestesia Local , Descompressão Cirúrgica , Endoscopia , Fraturas por Osteoporose , Fraturas da Coluna Vertebral , Estenose Espinal , Humanos , Feminino , Idoso de 80 Anos ou mais , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/etiologia , Estenose Espinal/cirurgia , Estenose Espinal/diagnóstico por imagem , Descompressão Cirúrgica/métodos , Endoscopia/métodos , Fraturas por Osteoporose/cirurgia , Fraturas por Osteoporose/diagnóstico por imagem , Vértebras Lombares/cirurgia , Vértebras Lombares/diagnóstico por imagem , Radiculopatia/cirurgia , Radiculopatia/etiologia
3.
J Orthop Sci ; 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38302309

RESUMO

BACKGROUND: Full-endoscopic spine surgery via a transforaminal approach (TF-FESS) is minimally invasive and could help athletes quickly return to play. When treating professional athletes, we have to consider their season schedule. In this study, we investigated the characteristics of Japanese professional baseball players who underwent TF-FESS and examine how the timing of surgery influenced their postoperative course. METHODS: Ten players who underwent TF-FESS (discectomy, foraminoplasty, or thermal annuloplasty according to their diagnosis) under local anesthesia were analyzed. Multilevel surgeries were performed at the same time in patients with lesions at multiple levels. The patients were divided into three groups according to timing of surgery (pre/during/post-season). Time to complete return to play and duration of official game loss were compared between the three groups. RESULTS: All players (100 %) could return to their original level of professional play after FESS surgery. Seven of the 10 patients underwent two-level surgery. The mean time until complete return to play was 4.6 months (range, 2-8 months) and the mean duration of game loss was 1.5 months (range, 0-4 months). The mean duration of game loss was shorter in the post-season group than in the other groups (0.9 vs 2,4 months), and 4 of 6 patients in the post-season group did not miss any games. CONCLUSIONS: TF-FESS is a good technique for achieving a quick return to play in professional baseball players. In particular, surgery performed during the post-season could allow players to return to play after adequate rehabilitation with no game loss.

4.
Heart ; 110(6): 441-447, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-37827559

RESUMO

OBJECTIVE: The heterogeneous pathophysiology of the diverse heart failure with preserved ejection fraction (HFpEF) phenotypes needs to be examined. We aim to assess differences in the biomarkers among the phenotypes of HFpEF and investigate its multifactorial pathophysiology. METHODS: This study is a retrospective analysis of the PURSUIT-HFpEF Study (N=1231), an ongoing, prospective, multicentre observational study of acute decompensated HFpEF. In this registry, there is a predefined subcohort in which we perform multibiomarker tests (N=212). We applied the previously established machine learning-based clustering model to the subcohort with biomarker measurements to classify them into four phenotypes: phenotype 1 (n=69), phenotype 2 (n=49), phenotype 3 (n=41) and phenotype 4 (n=53). Biomarker characteristics in each phenotype were evaluated. RESULTS: Phenotype 1 presented the lowest value of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive C reactive protein, tumour necrosis factor-α, growth differentiation factor (GDF)-15, troponin T and cystatin C, whereas phenotype 2, which is characterised by hypertension and cardiac hypertrophy, showed the highest value of these markers. Phenotype 3 showed the second highest value of GDF-15 and cystatin C. Phenotype 4 presented a low NT-proBNP value and a relatively high GDF-15. CONCLUSIONS: Distinctive characteristics of biomarkers in HFpEF phenotypes would indicate differential underlying mechanisms to be elucidated. The contribution of inflammation to the pathogenesis varied considerably among different HFpEF phenotypes. Systemic inflammation substantially contributes to the pathophysiology of the classic HFpEF phenotype with cardiac hypertrophy. TRIAL REGISTRATION NUMBER: UMIN-CTR ID: UMIN000021831.


Assuntos
Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/diagnóstico , Fator 15 de Diferenciação de Crescimento , Cistatina C , Volume Sistólico/fisiologia , Estudos Retrospectivos , Estudos Prospectivos , Biomarcadores , Peptídeo Natriurético Encefálico , Inflamação , Fragmentos de Peptídeos , Cardiomegalia , Prognóstico
5.
J Occup Med Toxicol ; 18(1): 27, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38037166

RESUMO

BACKGROUND: Fluoroscopy is indispensable when determining appropriate and effective interventions in orthopedic surgery. On the other hand, there is growing concern about the health hazards of occupational radiation exposure. The aim of this cadaveric simulation study was to measure radiation exposure doses to the surgical team during hip surgery. METHODS: We reproduced the intraoperative setting of hip surgery using 7 fresh frozen cadavers (5 male, 2 female) to simulate patients and mannequins to simulate the surgeon, scrub nurse, and anesthesiologist. Six real-time dosimeters were mounted at sites corresponding to the optic lens, thyroid gland, chest, gonads, foot, and hand on each mannequin. The radiation exposure dose to each team member was measured during posteroanterior and lateral fluoroscopic imaging. RESULTS: Radiation exposure doses to the surgeon were significantly higher during 3 min of lateral imaging than during 3 min of posteroanterior imaging at the optic lens (8.1 times higher), thyroid gland (10.3 times), chest (10.8 times), and hand (19.8 times) (p = 0.018, p = 0.018, p = 0.018, and p = 0.018, respectively). During lateral imaging, the radiation doses to the nurse were 0.16, 0.12, 0.09, 0.72, and 0.38 times those to the surgeon at the optic lens, thyroid, chest, gonads, and foot, respectively. The radiation dose to the anesthesiologist was zero at all anatomic sites during posteroanterior imaging and very small during lateral imaging. CONCLUSIONS: Radiation exposure dose was significantly higher during lateral imaging up to 19.8 times comparing to the posteroanterior imaging. It is effective to reduce the lateral imaging time for reducing the intraoperative radiation exposure. In addition, appropriate distance from fluoroscopy resulted in very low exposure for nurses and anesthesiologists. Surgeon should pay attention that surgical staff do not get closer than necessary to the irradiation field.

6.
World Neurosurg ; 178: 317-329, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37453727

RESUMO

Full-endoscopic (FE) lumbar interbody fusion (LIF) is now a widely used type of minimally invasive surgery (MIS). Although FE-LIF includes LIF with foraminoplasty via a Kambin's triangle approach (FE-KLIF) and LIF with foraminotomy via an interlaminar approach, these techniques are rarely discussed separately. This review evaluates the outcomes and complications of FE-KLIF reported in the literature. The PubMed, Medline, Embase, Web of Science, and Cochrane Library databases were searched for studies reporting the outcomes of FE-KLIF. Of 464 publications assessed, 11 met our inclusion criteria. Although the most frequently treated level was L4/5, L5/S1 was also treated. FE-KLIF was performed under local anesthesia and sedation or under epidural anesthesia without general anesthesia. Visual analog scale and Oswestry Disability Index scores were improved postoperatively in all uncontrolled studies; however, there was no significant difference in these scores in studies that compared FE-KLIF with posterior LIF (PLIF) or MIS-transforaminal LIF (TLIF). There was also no significant difference in the fusion rate between FE-KLIF and PLIF or MIS-TLIF. In terms of complications, although there were no reports of hematoma, dural tear and surgical site infection were reported in 1 paper each, with transient nerve disorders reported in 5 studies (frequency, 1.8%-23.5%). This review indicates that FE-KLIF is a feasible and viable surgical option for lumbar degenerative disease. However, the amount and level of evidence is low for the studies included in this review, and the data on long-term outcomes remain limited.

7.
NMC Case Rep J ; 10: 87-92, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37131495

RESUMO

Various approaches to lumbar interbody fusion have been described. The usefulness of full-endoscopic trans-Kambin's triangle lumbar interbody fusion has recently been reported. This technique has several advantages in patients with degenerative spondylolisthesis, including the ability to improve symptoms without decompression surgery. Moreover, given that the entire procedure is performed percutaneously, it can be performed without increasing the operation time or surgical invasiveness, even in obese patients. In this article, we discuss these advantages and illustrate them with representative cases.

8.
Cancer Med ; 12(8): 9668-9683, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36722116

RESUMO

BACKGROUND: Synovial sarcoma (SS) has limited treatment options and there is an urgent need to develop a novel therapeutic strategy to treat SS. Blue light (BL) has been shown to inhibit the growth of several cancer cells. However, the efficacy of BL in soft tissue sarcomas such as SS has not been demonstrated, and the detailed mechanism underlying the antitumor activity of BL is not fully understood. In this study, we investigated the antitumor effect of BL on SS. METHODS: Human SS cell lines were continuously irradiated with BL using light-emitting diodes (LEDs) in an incubator for in vitro analysis. The chicken chorioallantoic membrane (CAM) tumors and xenograft tumors in mice were subjected to daily BL irradiation with LEDs. RESULTS: BL caused growth inhibition of SS cells and histological changes in CAM tumors. BL also suppressed the migration and invasion abilities of SS cells. The type of cell death in SS cells was revealed to be apoptosis. Furthermore, BL induced excessive production of reactive oxygen species (ROS) in mitochondria, resulting in oxidative stress and malfunctioned mitochondria. Reducing the production of ROS using N-acetylcysteine (NAC), a ROS scavenger, attenuated the inhibitory effect of BL on SS cells and mitochondrial dysfunction. In addition, BL induced autophagy, which was suppressed by the administration of NAC. The autophagy inhibitor of 3-methyladenine and small interfering RNA against the autophagy marker light chain 3B facilitated apoptotic cell death. Moreover, BL suppressed tumor growth in a mouse xenograft model. CONCLUSION: Taken together, our results revealed that BL induced apoptosis via the ROS-mitochondrial signaling pathway, and autophagy was activated in response to the production of ROS, which protected SS cells from apoptosis. Therefore, BL is a promising candidate for the development of an antitumor therapeutic strategy targeting SS.


Assuntos
Sarcoma Sinovial , Humanos , Camundongos , Animais , Espécies Reativas de Oxigênio/metabolismo , Sarcoma Sinovial/terapia , Sarcoma Sinovial/patologia , Apoptose , Autofagia , Mitocôndrias , Linhagem Celular Tumoral
9.
Int J Cardiol ; 378: 55-63, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36796493

RESUMO

BACKGROUNDS: Drug treatments of heart failure with preserved ejection fraction (HFpEF) have a little clinical benefit, but cardiovascular polypharmacy (CP) trend is observed in elderly HFpEF. We investigated the impact of CP on octogenarian with HFpEF. METHODS: We examined 783 consecutive octogenarians (≥80 years) enrolled in the PURSUIT-HFpEF registry. We defined medications for hypertension, dyslipidemia, heart failure (HF), coronary artery disease, stroke, peripheral artery disease, and atrial fibrillation as cardiovascular medications (CM). In this study, we defined CP as ≥5 CM. We investigated whether CP was correlated with the composite end point (CE) of all-cause mortality and HF rehospitalization. RESULTS: The proportion with CP was 51.9% (n = 406). Background characteristics correlated with CP were frailty, history of coronary artery disease, atrial fibrillation and left atrial dimension. Multivariable Cox proportional hazards analysis showed CP was significantly and independently correlated with CE (hazard ratio (HR): 1.31; 95% confidence Interval (CI): 1.01-1.70) in addition to age, clinical frailty scale, history of HF admission and N-terminal pro brain natriuretic peptide. Kaplan-Meier curve analysis showed that, compared with the non-CP group, the CP group had significantly higher risk of CE and HF (HR: 1.27; 95%CI: 1.04-1.56; P = 0.02 and HR: 1.46; 95%CI: 1.13-1.88; P < 0.01, respectively), but not any-cause death. In addition, diuretics were correlated with CE (HR: 1.61; 95%CI: 1.17-2.22; P < 0.01), but antithrombotic drugs and HFpEF medications were not. CONCLUSIONS: CP at discharge is a prognostic factor driven by HF rehospitalization in octogenarians with HFpEF. In these patients, diuretics may be correlated with the prognosis.


Assuntos
Fibrilação Atrial , Doença da Artéria Coronariana , Fragilidade , Insuficiência Cardíaca , Idoso de 80 Anos ou mais , Humanos , Idoso , Prognóstico , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Volume Sistólico , Octogenários , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Função Ventricular Esquerda , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/tratamento farmacológico , Polimedicação , Diuréticos/uso terapêutico
10.
J Am Heart Assoc ; 10(20): e023043, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34612057

RESUMO

Background Although the prognostic importance of pulmonary arterial capacitance (PAC; stroke volume/pulmonary arterial pulse pressure) has been elucidated in heart failure with reduced ejection fraction, whether its significance in patients suffering from heart failure with preserved ejection fraction is not known. We aimed to examine the association of PAC with outcomes in inpatients with heart failure with preserved ejection fraction. Methods and Results We prospectively studied 705 patients (median age, 83 years; 55% women) registered in PURSUIT-HFpEF (Prospective Multicenter Observational Study of Patients With Heart Failure With Preserved Ejection Fraction). We investigated the association of echocardiographic PAC at discharge with the primary end point of all-cause death or heart failure rehospitalization with a mean follow-up of 384 days. We further tested the acceptability of the prognostic significance of PAC in a subgroup of patients (167/705 patients; median age, 81 years; 53% women) in whom PAC was assessed by right heart catheterization. The median echocardiographic PAC was 2.52 mL/mm Hg, with a quartile range of 1.78 to 3.32 mL/mm Hg. Univariable and multivariable Cox regression testing revealed that echocardiographic PAC was associated with the primary end point (unadjusted hazard ratio, 0.82; 95% CI, 0.72-0.92; P=0.001; adjusted hazard ratio, 0.86; 95% CI, 0.74-0.99; P=0.035, respectively). Univariable Cox regression testing revealed that PAC assessed by right heart catheterization (median calculated PAC, 2.82 mL/mm Hg) was also associated with the primary end point (unadjusted HR, 0.70; 95% CI, 0.52-0.91; P=0.005). Conclusions A prospective cohort study revealed that impaired PAC diagnosed with both echocardiography and right heart catheterization was associated with adverse outcomes in inpatients with heart failure with preserved ejection fraction. Registration URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000024414. Unique identifier: UMIN000021831.


Assuntos
Insuficiência Cardíaca , Hipertensão Pulmonar , Artéria Pulmonar , Capacitância Vascular , Idoso de 80 Anos ou mais , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Prognóstico , Estudos Prospectivos , Artéria Pulmonar/fisiopatologia , Volume Sistólico , Capacitância Vascular/fisiologia , Função Ventricular Esquerda
11.
Am J Clin Nutr ; 110(2): 330-339, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31161211

RESUMO

BACKGROUND: Nutritional status is associated with poor outcomes in patients with heart failure. Serum cholinesterase (CHE) concentration, a marker of malnutrition, was reported to be a prognostic factor in patients with chronic heart failure. The geriatric nutritional risk index (GNRI), the controlling nutritional status (CONUT) score, and the prognostic nutritional index (PNI) are established objective nutritional indices. OBJECTIVE: The aim of this study was to clarify the prognostic significance of CHE concentration and to compare it with other well-established objective nutritional indices in patients with acute decompensated heart failure (ADHF). METHODS: We prospectively enrolled 371 consecutive patients admitted for ADHF with survival discharge. Laboratory data including CHE and the objective nutritional indices were obtained at discharge. The primary endpoint of this study was all-cause mortality. RESULTS: During a mean ± SD follow-up period of 2.5 ± 1.4 y, 112 patients died. CHE concentration was significantly associated with all-cause mortality independently of GNRI, CONUT score, or PNI, after adjustment for major confounders including other nutritional indices, such as age, sex, systolic blood pressure, BMI, left ventricular ejection fraction, history of hypertension, diabetes mellitus, dyslipidemia, prior heart failure hospitalization, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, ß-blocker use, statin use, hemoglobin, sodium, blood urea nitrogen, albumin, C-reactive protein, and brain natriuretic peptide concentrations via multivariable Cox analysis. Kaplan-Meier analysis revealed that the risk of all-cause mortality significantly increased in accordance with CHE stratum [lowest tertile: 53%, adjusted HR: 6.92; 95% CI: 3.87, 12.36, compared with middle tertile: 28%, adjusted HR: 2.72; 95% CI: 1.45, 5.11, compared with highest tertile: 11%, adjusted HR: 1.0 (reference), P < 0.0001]. CHE showed the best area under the curve value (0.745) for the prediction of all-cause mortality compared with the other objective nutritional indices. Net reclassification improvement afforded by adding CHE to the fully adjusted multivariable model was statistically significant for all-cause mortality (0.330; 95% CI: 0.112, 0.549, P = 0.0030). CONCLUSION: CHE is a simple, strong prognostic marker for the prediction of all-cause mortality in patients with ADHF.


Assuntos
Colinesterases/sangue , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/patologia , Estado Nutricional , Idoso , Idoso de 80 Anos ou mais , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco
12.
Arthroscopy ; 34(1): 105-110, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28866343

RESUMO

PURPOSE: To evaluate the clinical outcomes of arthroscopic treatment in adolescent baseball players with posteromedial elbow impingement. METHODS: This retrospective study evaluated the clinical outcome of arthroscopic treatment for posteromedial elbow impingement in adolescent baseball players. Patients were eligible for participation if they had undergone surgery at least 2 years earlier and excluded if they had arthritis, loose bodies, osteochondritis dissecans, ulnar collateral ligament tear, flexor/pronator injuries or medial epicondylitis, or nerve problems. Patients were also excluded if they had undergone prior elbow surgery, were younger than 13 years, or were older than 19 years. Arthroscopic treatment included debridement of posteromedial synovitis, fragment removal, and olecranon spur excision. At a mean follow-up of 26.7 (range 24-42) months, patients were evaluated based on a questionnaire, examination, and the previously reported elbow outcome score. RESULTS: This retrospective study involved 15 male patients, comprising 6 pitchers, 3 catchers, and 6 fielders, of mean age 15.7 (range 14-17) years. Mean time from onset of symptoms to surgery was 4.9 (range 3-18) months. Intraoperative findings included posteromedial synovitis and olecranon spurs in all patients and fragments in 10. The elbow outcome score was considered excellent in 11 patients and good in 2, with a mean score of 92 points (maximum 100 points). The mean postoperative range of motion at the elbow was 5° to 139.7° of flexion. All patients were able to return to their previous level of play after an average of 3.4 (range 2.5-4.5) months. No patient developed medial instability that later required reconstructive surgery. CONCLUSIONS: Arthroscopic debridement, excision of the olecranon spur, and removal of fragments yield reliable subjective and objective results and allow a return to baseball in adolescent patients. LEVEL OF EVIDENCE: Level IV, therapeutic case series.


Assuntos
Artralgia/cirurgia , Artroscopia/métodos , Traumatismos em Atletas/cirurgia , Beisebol/lesões , Ligamento Colateral Ulnar/lesões , Desbridamento/métodos , Articulação do Cotovelo/cirurgia , Adolescente , Artralgia/etiologia , Feminino , Humanos , Masculino , Amplitude de Movimento Articular , Estudos Retrospectivos , Resultado do Tratamento , Lesões no Cotovelo
13.
J Med Invest ; 63(1-2): 131-4, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27040068

RESUMO

Os acromiale is a rare anatomical variant that is caused by failure of fusion of the acromial apophysis and is usually asymptomatic. We report a case of impingement syndrome of the left shoulder secondary to unstable os acromiale, which was initially overlooked and confirmed only during arthroscopic examination. Arthroscopic excision of the unstable fragment was successful without residual dysfunction of the deltoid muscle.


Assuntos
Acrômio/anormalidades , Síndrome de Colisão do Ombro/diagnóstico por imagem , Acrômio/diagnóstico por imagem , Acrômio/cirurgia , Idoso , Artroscopia , Feminino , Humanos , Imageamento por Ressonância Magnética , Síndrome de Colisão do Ombro/etiologia , Síndrome de Colisão do Ombro/cirurgia , Tomografia Computadorizada por Raios X
14.
Yonago Acta Med ; 57(3): 109-16, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25349466

RESUMO

BACKGROUND: Cardiac fibrosis is considered to be a crucial factor in the development of heart failure. Blockade of the mineralocorticoid receptor (MR) attenuated cardiac fibrosis and improved the prognosis of patients with chronic heart failure but the ligand for MR and the regulatory mechanism of MR pathway in the diseased heart are unclear. Here, we investigated whether glucocorticoids can promote cardiac fibrosis through MR in oxidative stress and the involvement of elongation factor eleven-nineteen lysine-rich leukemia (ELL), a co-activator of MR, in this pathway. METHODS AND RESULTS: The MR antagonist eplerenone attenuated corticosterone-induced collagen synthesis assessed by [(3)H]proline incorporation in rat neonatal cultured cardiac fibroblasts in the presence of H2O2, as an oxidative stress but not in the absence of H2O2. H2O2 increased the ELL expression levels and MR-bound ELL. ELL expression levels and MR-bound ELL were also increased in the left ventricle of heart failure model rats with significant fibrosis and enhanced oxidative stress. Eplerenone did not attenuate corticosterone-induced increase of [(3)H]proline incorporation in the presence of H2O2 after knockdown of ELL expression using small interfering RNA in cardiac fibroblasts. CONCLUSION: Glucocorticoids can promote cardiac fibrosis via MR in oxidative stress, and oxidative stress modulates MR response to glucocorticoids through the interaction with ELL. Preventing cardiac fibrosis by modulating glucocorticoid-MR-ELL pathway may become a new therapeutic strategy for heart failure.

15.
PLoS One ; 8(7): e68893, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23894370

RESUMO

BACKGROUND: Chronic heart failure (CHF) with preserved left ventricular (LV) ejection fraction (HFpEF) is observed in half of all patients with CHF and carries the same poor prognosis as CHF with reduced LV ejection fraction (HFrEF). In contrast to HFrEF, there is no established therapy for HFpEF. Chronic inflammation contributes to cardiac fibrosis, a crucial factor in HFpEF; however, inflammatory mechanisms and mediators involved in the development of HFpEF remain unclear. Therefore, we sought to identify novel inflammatory mediators involved in this process. METHODS AND RESULTS: An analysis by multiplex-bead array assay revealed that serum interleukin-16 (IL-16) levels were specifically elevated in patients with HFpEF compared with HFrEF and controls. This was confirmed by enzyme-linked immunosorbent assay in HFpEF patients and controls, and serum IL-16 levels showed a significant association with indices of LV diastolic dysfunction. Serum IL-16 levels were also elevated in a rat model of HFpEF and positively correlated with LV end-diastolic pressure, lung weight and LV myocardial stiffness constant. The cardiac expression of IL-16 was upregulated in the HFpEF rat model. Enhanced cardiac expression of IL-16 in transgenic mice induced cardiac fibrosis and LV myocardial stiffening accompanied by increased macrophage infiltration. Treatment with anti-IL-16 neutralizing antibody ameliorated cardiac fibrosis in the mouse model of angiotensin II-induced hypertension. CONCLUSION: Our data indicate that IL-16 is a mediator of LV myocardial fibrosis and stiffening in HFpEF, and that the blockade of IL-16 could be a possible therapeutic option for HFpEF.


Assuntos
Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Interleucina-16/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Volume Sistólico , Idoso , Idoso de 80 Anos ou mais , Animais , Modelos Animais de Doenças , Feminino , Fibrose , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Hemodinâmica , Humanos , Hipertensão/complicações , Interleucina-16/sangue , Interleucina-16/genética , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Camundongos Transgênicos , Pessoa de Meia-Idade , Ratos , Fatores de Risco , Volume Sistólico/genética , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/fisiopatologia
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