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1.
Circulation ; 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38666382

RESUMO

BACKGROUND: The clinical application of human induced pluripotent stem cell-derived cardiomyocytes (CMs) for cardiac repair commenced with the epicardial delivery of engineered cardiac tissue; however, the feasibility of the direct delivery of human induced pluripotent stem cell-derived CMs into the cardiac muscle layer, which has reportedly induced electrical integration, is unclear because of concerns about poor engraftment of CMs and posttransplant arrhythmias. Thus, in this study, we prepared purified human induced pluripotent stem cell-derived cardiac spheroids (hiPSC-CSs) and investigated whether their direct injection could regenerate infarcted nonhuman primate hearts. METHODS: We performed 2 separate experiments to explore the appropriate number of human induced pluripotent stem cell-derived CMs. In the first experiment, 10 cynomolgus monkeys were subjected to myocardial infarction 2 weeks before transplantation and were designated as recipients of hiPSC-CSs containing 2×107 CMs or the vehicle. The animals were euthanized 12 weeks after transplantation for histological analysis, and cardiac function and arrhythmia were monitored during the observational period. In the second study, we repeated the equivalent transplantation study using more CMs (6×107 CMs). RESULTS: Recipients of hiPSC-CSs containing 2×107 CMs showed limited CM grafts and transient increases in fractional shortening compared with those of the vehicle (fractional shortening at 4 weeks after transplantation: 26.2±2.1%; 19.3±1.8%; P<0.05), with a low incidence of posttransplant arrhythmia. Transplantation of increased dose of CMs resulted in significantly greater engraftment and long-term contractile benefits (fractional shortening at 12 weeks after transplantation: 22.5±1.0%; 16.6±1.1%; P<0.01, left ventricular ejection fraction at 12 weeks after transplantation: 49.0±1.4%; 36.3±2.9%; P<0.01). The incidence of posttransplant arrhythmia slightly increased in recipients of hiPSC-CSs containing 6×107 CMs. CONCLUSIONS: We demonstrated that direct injection of hiPSC-CSs restores the contractile functions of injured primate hearts with an acceptable risk of posttransplant arrhythmia. Although the mechanism for the functional benefits is not fully elucidated, these findings provide a strong rationale for conducting clinical trials using the equivalent CM products.

2.
J Mol Cell Cardiol ; 174: 77-87, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36403760

RESUMO

Advances in stem cell biology have facilitated cardiac regeneration, and many animal studies and several initial clinical trials have been conducted using human pluripotent stem cell-derived cardiomyocytes (PSC-CMs). Most preclinical and clinical studies have typically transplanted PSC-CMs via the following two distinct approaches: direct intramyocardial injection or epicardial delivery of engineered heart tissue. Both approaches present common disadvantages, including a mandatory thoracotomy and poor engraftment. Furthermore, a standard transplantation approach has yet to be established. In this study, we tested the feasibility of performing intracoronary administration of PSC-CMs based on a commonly used method of transplanting somatic stem cells. Six male cynomolgus monkeys underwent intracoronary administration of dispersed human PSC-CMs or PSC-CM aggregates, which are called cardiac spheroids, with multiple cell dosages. The recipient animals were sacrificed at 4 weeks post-transplantation for histological analysis. Intracoronary administration of dispersed human PSC-CMs in the cynomolgus monkeys did not lead to coronary embolism or graft survival. Although the transplanted cardiac spheroids became partially engrafted, they also induced scar formation due to cardiac ischemic injury. Cardiac engraftment and scar formation were reasonably consistent with the spheroid size or cell dosage. These findings indicate that intracoronary transplantation of PSC-CMs is an inefficient therapeutic approach.


Assuntos
Miócitos Cardíacos , Células-Tronco Pluripotentes , Animais , Humanos , Masculino , Cicatriz/patologia , Macaca fascicularis , Miócitos Cardíacos/patologia , Células-Tronco Pluripotentes/patologia
3.
Heart Vessels ; 38(3): 438-447, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36205773

RESUMO

This study aimed to investigate the relationship between heart rate variability (HRV), a parameter of the autonomic nervous system activity (ANSA), and postoperative delirium and postoperative events. This retrospective cohort study included elderly patients aged 65 years or older who were admitted to the intensive care unit (ICU) after cardiovascular surgery. ANSA was measured using HRV parameters for 1 h at daytime and 1 h at night-time before ICU discharge. The primary endpoint was the effect of HRV parameters and delirium on mortality and readmission rates within 1 year after discharge, and the secondary endpoint was the association between HRV parameters and delirium. Cox proportional hazards models were used to examine the association between HRV parameters and postoperative events by adjusting for delirium and pre and postoperative information. A total of 71 patients, 39 without delirium and 32 with delirium, met the inclusion criteria. The incidence of death and readmission within 1 year was significantly higher in the delirium group and in the group with higher daytime HF (high frequency power) and r-MSSD (square root of the squared mean of the difference of successive NN intervals), parameters of the parasympathetic nervous system activity (PNSA), than that in other groups. Furthermore, the delirium group had significantly higher HF and r-MSSD than the nondelirium group. Even after adjusting for confounding factors in the multivariate analysis, a trend of higher daytime HF and r-MSSD was observed, indicating a significant effect on the occurrence of combined events within 1 year of discharge. ICU delirium has been associated with higher daytime HF and r-MSSD, parameters of PNSA. ICU delirium was a prognostic factor, and increased daytime PNSA may worsen the prognosis of elderly patients after cardiovascular surgery.


Assuntos
Delírio do Despertar , Idoso , Humanos , Frequência Cardíaca/fisiologia , Readmissão do Paciente , Estudos Retrospectivos , Unidades de Terapia Intensiva
4.
J Artif Organs ; 26(4): 297-302, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36348184

RESUMO

PURPOSE: Fulminant myocarditis presents as acute severe heart failure and requires mechanical cardiocirculatory support. Left-ventricular (LV) decompression is necessary for the successful recovery of these patients. This retrospective study aimed to evaluate the functional outcomes of providing central extracorporeal membrane oxygenation (ECMO) with LV decompression for the treatment of refractory fulminant myocarditis. METHODS: Between January 2015 and February 2021, seven consecutive fulminant myocarditis patients (mean age: 41.1 ± 26.1 years) received central ECMO support with transapical LV decompression, with an 18 French cannula integrated into the ECMO circuit in a Y-fashion. The baseline characteristics and postoperative outcomes of the patients were collected. RESULTS: On admission, all patients received prior peripheral ECMO, and 85.7% (6/7) of patients received prior intra-aortic balloon pumping. However, all patients had refractory cardiogenic shock that failed prior to decompression. Six patients recovered successfully after a mean ECMO support of 20.0 ± 11.5 days and five patients had no recurrence of cardiac decompensation. The mean ICU and mean hospital stays were 36.7 ± 23.5 days and 60.6 ± 24.9 days, respectively. Hospital mortality was 28.6% (2/7). Two patients died due to sepsis and stroke during hospitalization. CONCLUSIONS: Central ECMO with an LV vent was effective for fulminant myocarditis refractory to percutaneous cardiopulmonary support therapy and other therapies.


Assuntos
Oxigenação por Membrana Extracorpórea , Insuficiência Cardíaca , Miocardite , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Miocardite/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Coração , Choque Cardiogênico/etiologia , Choque Cardiogênico/cirurgia
5.
Kyobu Geka ; 76(10): 769-773, 2023 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-38056834

RESUMO

Chronic kidney disease( CKD) is a challenge in cardiac surgery in elderly patients, making intraoperative and postoperative management critical. Although sodium glucose co-transporter 2( SGLT2) inhibitors have nephroprotective effects, it's important to discontinue them three days before surgery and resume them when food intake is possible. Nephroprotective perioperative management of CKD stage 3-4 patients requires different approaches at each stage, with blood pressure control and nutritional counseling being key. For patients with CKD stage 5, postoperative management includes circulatory management in the intensive care unit and assessment of the need for and timing of hemodialysis. Continuous renal replacement therapy( CRRT) is common, but recently the use of multiple dialysis modalities (multimodal approach) has increased. This multimodal approach, which aims to avoid CRRT trauma, may contribute to improved outcomes.


Assuntos
Falência Renal Crônica , Insuficiência Renal Crônica , Idoso , Humanos , Unidades de Terapia Intensiva , Diálise Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Monitorização Intraoperatória , Cuidados Pós-Operatórios
6.
Nature ; 538(7625): 388-391, 2016 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-27723741

RESUMO

Induced pluripotent stem cells (iPSCs) constitute a potential source of autologous patient-specific cardiomyocytes for cardiac repair, providing a major benefit over other sources of cells in terms of immune rejection. However, autologous transplantation has substantial challenges related to manufacturing and regulation. Although major histocompatibility complex (MHC)-matched allogeneic transplantation is a promising alternative strategy, few immunological studies have been carried out with iPSCs. Here we describe an allogeneic transplantation model established using the cynomolgus monkey (Macaca fascicularis), the MHC structure of which is identical to that of humans. Fibroblast-derived iPSCs were generated from a MHC haplotype (HT4) homozygous animal and subsequently differentiated into cardiomyocytes (iPSC-CMs). Five HT4 heterozygous monkeys were subjected to myocardial infarction followed by direct intra-myocardial injection of iPSC-CMs. The grafted cardiomyocytes survived for 12 weeks with no evidence of immune rejection in monkeys treated with clinically relevant doses of methylprednisolone and tacrolimus, and showed electrical coupling with host cardiomyocytes as assessed by use of the fluorescent calcium indicator G-CaMP7.09. Additionally, transplantation of the iPSC-CMs improved cardiac contractile function at 4 and 12 weeks after transplantation; however, the incidence of ventricular tachycardia was transiently, but significantly, increased when compared to vehicle-treated controls. Collectively, our data demonstrate that allogeneic iPSC-CM transplantation is sufficient to regenerate the infarcted non-human primate heart; however, further research to control post-transplant arrhythmias is necessary.


Assuntos
Coração/fisiologia , Células-Tronco Pluripotentes Induzidas/citologia , Infarto do Miocárdio/terapia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/transplante , Regeneração/fisiologia , Animais , Diferenciação Celular , Sobrevivência Celular , Feminino , Fibroblastos/citologia , Sobrevivência de Enxerto , Haplótipos , Imunossupressores , Macaca fascicularis , Complexo Principal de Histocompatibilidade/genética , Masculino , Contração Miocárdica/fisiologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miócitos Cardíacos/imunologia , Miócitos Cardíacos/metabolismo , Taquicardia Ventricular/etiologia , Taquicardia Ventricular/fisiopatologia , Fatores de Tempo , Transplante Homólogo
7.
Int Heart J ; 63(2): 404-407, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35296613

RESUMO

An aortic valve with a coronary cusp adherent to the aortic wall is a rare anomaly. Furthermore, an adherent coronary cusp with fenestration is even rarer. Here, we report a case of aortic valve regurgitation with an adherent and fenestrated left coronary cusp. A 45-year-old man with complaints of dyspnea on exertion was hospitalized. Clinical examination revealed severe aortic valve regurgitation associated with poor cardiac function. He had a history of cardiac murmur present since childhood; however, the details of his cardiac history are unknown. During surgery, a fenestrated left coronary cusp adherent to the aortic wall was observed. Following resection of all aortic cusps, we performed an aortic valve replacement with a mechanical valve. The postoperative recovery was uneventful. In this case, the left coronary artery was perfused by a small fenestration in the adherent coronary cusp. In such cases, the adherent coronary cusp should be released to alleviate the possibility of sudden death and ischemic myocarditis.


Assuntos
Insuficiência da Valva Aórtica , Próteses Valvulares Cardíacas , Aorta/diagnóstico por imagem , Aorta/cirurgia , Valva Aórtica/anormalidades , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/cirurgia , Criança , Humanos , Masculino , Pessoa de Meia-Idade
8.
Kyobu Geka ; 75(8): 593-597, 2022 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-35892297

RESUMO

A 41-year-old man stuck himself with needle through his pericardium during suicide attempt. Chest radiography revealed several needles in the bilateral lung fields as well. Computed tomography (CT) and echocardiography showed massive pericardial effusion and a needle penetrating the pericardium. The patient was initially treated conservatively, including pericardial drainage, and, seven days later, we removed the needle using syngo Needle Guidance in hybrid operating room. The length of skin incision was only 2 cm, and the postoperative course was uneventful. No previous studies, to the best of our knowledge, have shown the use of syngo Needle Guidance to remove a needle in the pericardial cavity. This surgical procedure is minimally invasive for the patient.


Assuntos
Derrame Pericárdico , Adulto , Humanos , Masculino , Agulhas , Paracentese , Derrame Pericárdico/terapia , Pericárdio/cirurgia , Tomografia Computadorizada por Raios X
9.
Pflugers Arch ; 473(10): 1657-1666, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34251510

RESUMO

We demonstrated pulmonary arteriolar blood flow-mediated CO2 gas excretion in rabbit lungs. The shear stress stimulation produced CO2 gas in cultured human endothelial cells of pulmonary arterioles via the activation of F1/Fo ATP synthase. To confirm the findings in human subjects undergoing the operation with heart-lung machines, we aimed to evaluate the effects of a stepwise switch, from a partial to a complete cardiopulmonary bypass, of the circulatory blood volume (BV, 100% = 2.4 × cardiac index), on the end-expiratory CO2 pressure (PetCO2), maximal flow velocity in the pulmonary artery (Max Vp), the inner diameter (ID) of pulmonary artery, pulmonary arterial CO2 pressure (P mix v CO2), pulmonary arterial O2 pressure (P mix v O2), hematocrit (Hct), pH, the concentration of HCO3-, and base excess (BE) in mixed venous blood in 9 patients with a mean age of 72.3 ± 3.4 years. In addition, the effects of the decrease in Hct infused with physiological saline solution (PSS) on PetCO2 were investigated in the human subjects. An approximately linear relationship between the PetCO2 and Max Vp was observed. The pumping out of 100% BV produced little or no change in the Hct, pH, P mix v CO2, and P mix v O2, respectively. The hemodilution produced by intravenous infusion of PSS caused a significant decrease in the Hct, but not in the PetCO2. In conclusion, another route of CO2 gas excretion, independent of red blood cells, may be involved in human lungs.


Assuntos
Dióxido de Carbono/metabolismo , Eritrócitos/metabolismo , Circulação Pulmonar , Idoso , Ponte Cardiopulmonar , Feminino , Humanos , Pulmão , Masculino
10.
J Immunol ; 203(8): 2328-2338, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31541025

RESUMO

The T cell-specific adaptor protein (TSAd), encoded by the SH2D2A gene, is an intracellular molecule that binds Lck to elicit signals that result in cytokine production in CD4+ T effector cells (Teff). Nevertheless, using Sh2d2a knockout (KO; also called TSAd-/-) mice, we find that alloimmune CD4+ Teff responses are fully competent in vivo. Furthermore, and contrary to expectations, we find that allograft rejection is accelerated in KO recipients of MHC class II-mismatched B6.C-H-2bm12 heart transplants versus wild-type (WT) recipients. Also, KO recipients of fully MHC-mismatched cardiac allografts are resistant to the graft-prolonging effects of costimulatory blockade. Using adoptive transfer models, we find that KO T regulatory cells (Tregs) are less efficient in suppressing Teff function and they produce IFN-γ following mitogenic activation. In addition, pyrosequencing demonstrated higher levels of methylation of CpG regions within the Treg-specific demethylated region of KO versus WT Tregs, suggesting that TSAd, in part, promotes Treg stability. By Western blot, Lck is absent in the mitochondria of KO Tregs, and reactive oxygen species production by mitochondria is reduced in KO versus WT Tregs. Full transcriptomic analysis demonstrated that the key mechanism of TSAd function in Tregs relates to its effects on cellular activation rather than intrinsic effects on mitochondria/metabolism. Nevertheless, KO Tregs compensate for a lack of activation by increasing the number of mitochondria per cell. Thus, TSAd serves as a critical cell-intrinsic molecule in CD4+Foxp3+ Tregs to regulate the translocation of Lck to mitochondria, cellular activation responses, and the development of immunoregulation following solid organ transplantation.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Linfócitos T CD4-Positivos/imunologia , Mitocôndrias/metabolismo , Transplante , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Transferência Adotiva , Animais , Linfócitos T CD4-Positivos/citologia , Proliferação de Células , Células Cultivadas , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout
11.
Circ J ; 83(2): 424-431, 2019 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-30568052

RESUMO

BACKGROUND: Despite the best efforts of pediatricians, healthcare for adult patients with congenital heart disease (ACHD) has proven challenging because of the increased numbers. This study presents the process of establishing an ACHD care system as a collaborative effort between Shinshu University Hospital and Nagano Children's Hospital. Methods and Results: Establishing an outpatient clinic for transition, a cooperation agreement for in-patient care between the 2 hospitals, and quality management of diagnostic imaging and educational meetings for adult cardiologists were the 3 major challenges. Of the 99 patients who visited the transition clinic in the children's hospital between May 2014 and December 2016, 3 returned to the pediatrician's clinic. Between June 2013 and December 2017, 273 patients visited the ACHD center in Shinshu University Hospital. Until December 2017, mortality and fatal arrhythmia were noted in 3 and 2 cases, respectively. Catheter ablation for arrhythmia was performed in 12 cases, and 4 cases of pregnancy with moderate/severe ACHD or estimated as high risk were managed with healthy livebirths. Surgical interventions for moderate/severe ACHD were performed in collaboration with the children's hospital or Sakakibara Heart Institute. CONCLUSIONS: Patients were successfully transferred to adult cardiology departments. Surgical and nonsurgical interventions for ACHD were provided. Collaboration between adult and pediatric cardiologists assists in the establishment of healthcare systems for ACHD.


Assuntos
Atenção à Saúde/métodos , Cardiopatias Congênitas , Hospitais Pediátricos/organização & administração , Adulto , Cardiologistas , Cardiologia/métodos , Cardiologia/organização & administração , Serviço Hospitalar de Cardiologia , Criança , Atenção à Saúde/organização & administração , Feminino , Humanos , Colaboração Intersetorial , Masculino
13.
Ann Vasc Surg ; 47: 279.e1-279.e5, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28647628

RESUMO

Aneurysm of the proximal ulnar artery is extremely rare. Ultrasonography, computed tomography, and magnetic resonance imaging generally provide accurate diagnosis of aneurysm. A 29-year-old woman who had undergone an excision biopsy of a mass in her right arm by an orthopedic surgeon was referred to our department. We resected the mass and interposed it with a reversed great saphenous vein. Histopathological examination suggested that the mass was a pseudoaneurysm consisting of organized thrombi with recanalization. Clinicians should be aware of the possibility of misdiagnosis of soft tissue tumor in cases of pseudoaneurysm, especially if imaging examination reveals a density consistent with organized thrombus with recanalization.


Assuntos
Falso Aneurisma/diagnóstico por imagem , Imagem Multimodal/métodos , Neoplasias de Tecidos Moles/diagnóstico por imagem , Artéria Ulnar/diagnóstico por imagem , Adulto , Falso Aneurisma/patologia , Falso Aneurisma/cirurgia , Biópsia , Angiografia por Tomografia Computadorizada , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Valor Preditivo dos Testes , Veia Safena/transplante , Resultado do Tratamento , Artéria Ulnar/patologia , Artéria Ulnar/cirurgia , Ultrassonografia Doppler em Cores
14.
Tohoku J Exp Med ; 244(1): 53-62, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29353823

RESUMO

Critical limb ischemia (CLI) is the most severe complication of peripheral arterial disease (PAD). Understanding the molecular mechanisms underlying tissue repair after CLI is necessary for preventing PAD progression. Y-box binding protein-1 (YB-1) regulates the expression of many genes in response to environmental stresses. We aimed to determine whether YB-1 is involved in ischemic muscle regeneration. A mouse ischemic hind-limb model was generated; namely, the femoral, saphenous, and popliteal arteries in the left hind limb were ligated. The right hind limb, with skin incisions alone, served as control. Hind limbs (n = 3-5 for each time point) were examined on day 0 (before the operation) and on postoperative days 1, 2, 7, 10, and 14, and the biceps femoris, adductor, rectus femoris, and gracilis muscles were subjected to histopathological and immunohistochemical analyses. In ischemic limbs, myogenesis, triggered by an increase in myotubes, began on day 7; thereafter, regenerated muscles gradually increased in volume. RT-PCR analysis showed that YB-1 mRNA levels were increased in the limbs after ischemic injury, peaked on day 2, and subsequently decreased. On day 7, expression levels of MyoD and alpha-smooth muscle actin (αSMA) mRNAs were significantly higher in ischemic muscles than in control muscles. Immunohistochemical analysis revealed increased YB-1 immunoreactivity in myoblasts and myotubes on day 7, which was decreased by day 14. The immunoreactive αSMA and smooth muscle myosin heavy chain were transiently increased in myotubes. This is the first report showing the increased expression of YB-1 during muscle regeneration after ischemic injury.


Assuntos
Membro Posterior/irrigação sanguínea , Membro Posterior/patologia , Isquemia/metabolismo , Isquemia/patologia , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Regeneração , Proteína 1 de Ligação a Y-Box/metabolismo , Actinas/genética , Actinas/metabolismo , Animais , Masculino , Camundongos Endogâmicos BALB C , Desenvolvimento Muscular , Fibras Musculares Esqueléticas/metabolismo , Proteína MyoD/genética , Proteína MyoD/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Tempo
15.
Int Heart J ; 55(5): 463-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25070122

RESUMO

Cardiac tumors and tumor-like lesions are uncommon; most are true neoplasms. We here report a case of a pericoronary tumor-like lesion surrounding the right coronary artery in a 39-year-old man who presented with fever and chest pain. Although clarithromycin was administered for 1 week, his fever persisted. Helicobacter cinaedi (H. cinaedi) was isolated from blood cultures and found to be sensitive to ceftriaxone. A computed tomography scan showed a tumor-like lesion with no (18)F-fl uorodeoxyglucose uptake surrounding the right coronary artery. After administration of ceftriaxone, the tumor-like lesion diminished in size according to meticulous computed tomography examinations. We therefore concluded that it was caused by H. cinaedi infection. The patient has been followed up closely for 1 year and remains asymptomatic.


Assuntos
Granuloma de Células Plasmáticas/microbiologia , Cardiopatias/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter/isolamento & purificação , Adulto , Antibacterianos/administração & dosagem , Ceftriaxona/administração & dosagem , Vasos Coronários , Diagnóstico Diferencial , Granuloma de Células Plasmáticas/diagnóstico , Granuloma de Células Plasmáticas/tratamento farmacológico , Cardiopatias/diagnóstico , Cardiopatias/tratamento farmacológico , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/tratamento farmacológico , Humanos , Injeções Intravenosas , Imagem Cinética por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios X
16.
JVS Vasc Sci ; 4: 100123, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37662587

RESUMO

Objective: Synchrotron radiation-based X ray phase-contrast tomography (XPCT) was used in this study to evaluate abdominal aorta specimens from patients with sac expansion without evidence of an endoleak (endotension) following endovascular aortic repair (EVAR) for an abdominal aortic aneurysm (AAA). The aim of this study was to analyze the morphologic structure of the aortic wall in patients with this condition and to establish the cause of the endotension. Methods: Human aortic specimens of the abdominal aorta were obtained during open repair, fixed with formalin, and analyzed among three groups. Group A was specimens from open abdominal aortic aneurysm repairs (n = 7). Group E was specimens from sac expansion without an evident endoleak after EVAR (n = 7). Group N was specimens from non-aneurysmal "normal" cadaveric abdominal aortas (n = 5). Using XPCT (effective voxel size, 12.5 µm; density resolution, 1 mg/cm3), we measured the density of the tunica media (TM) in six regions of each sample. Then, any changes to the elastic lamina and the vasa vasorum were analyzed pathologically. The specimens were immunohistochemically examined with anti-CD31 and vascular endothelial growth factor antibodies. Results: The time from EVAR to open aortic repair was 64.2 ± 7.2 months. There were significant differences in the thickness of the TM among three groups: 0.98 ± 0.03 mm in Group N; 0.31 ± 0.01 mm in Group A; and 0.15 ± 0.03 mm in Group E (P < .005). There were significant differences in the TM density among the groups: 1.087 ± 0.004 g/cm3 in Group N; 1.070 ± 0.001 g/cm3 in Group A; and 1.062 ± 0.007 g/cm3 in Group E (P < .005). Differences in the thickness and density of the TM correlated with the thickness of the elastic lamina; in Group N, uniform high-density elastic fibers were observed in the TM. By contrast, a thinning of the elastic lamina in the TM was observed in Group A. A marked thinness and loss of elastic fibers was observed in Group E. CD31 immunostaining revealed that the vasa vasorum was localized in the adventitia and inside the outer third of the TM in Group N, and in the middle of the TM in Group A. In Group E, the vasa vasorum advanced up to the intima with vascular endothelial growth factor-positive cells in the intimal section. Conclusions: XPCT could be used to demonstrate the densitometric property of the aortic aneurysmal wall after EVAR. We confirmed that the deformation process that occurs in the sac expansion after EVAR without evidence of an endoleak could be explained by hypoxia in the aortic wall.

17.
Stem Cell Res Ther ; 14(1): 240, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37679796

RESUMO

BACKGROUND: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) can be used to treat heart diseases; however, the optimal maturity of hiPSC-CMs for effective regenerative medicine remains unclear. We aimed to investigate the benefits of long-term cultured mature hiPSC-CMs in injured rat hearts. METHODS: Cardiomyocytes were differentiated from hiPSCs via monolayer culturing, and the cells were harvested on day 28 or 56 (D28-CMs or D56-CMs, respectively) after differentiation. We transplanted D28-CMs or D56-CMs into the hearts of rat myocardial infarction models and examined cell retention and engraftment via in vivo bioluminescence imaging and histological analysis. We performed transcriptomic sequencing analysis to elucidate the genetic profiles before and after hiPSC-CM transplantation. RESULTS: Upregulated expression of mature sarcomere genes in vitro was observed in D56-CMs compared with D28-CMs. In vivo bioluminescence imaging studies revealed increased bioluminescence intensity of D56-CMs at 8 and 12 weeks post-transplantation. Histological and immunohistochemical analyses showed that D56-CMs promoted engraftment and maturation in the graft area at 12 weeks post-transplantation. Notably, D56-CMs consistently promoted microvessel formation in the graft area from 1 to 12 weeks post-transplantation. Transcriptomic sequencing analysis revealed that compared with the engrafted D28-CMs, the engrafted D56-CMs enriched genes related to blood vessel regulation at 12 weeks post-transplantation. As shown by transcriptomic and western blot analyses, the expression of a small heat shock protein, alpha-B crystallin (CRYAB), was significantly upregulated in D56-CMs compared with D28-CMs. Endothelial cell migration was inhibited by small interfering RNA-mediated knockdown of CRYAB when co-cultured with D56-CMs in vitro. Furthermore, CRYAB overexpression enhanced angiogenesis in the D28-CM grafts at 4 weeks post-transplantation. CONCLUSIONS: Long-term cultured mature hiPSC-CMs promoted engraftment, maturation and angiogenesis post-transplantation in infarcted rat hearts. CRYAB, which was highly expressed in D56-CMs, was identified as an angiogenic factor from mature hiPSC-CMs. This study revealed the benefits of long-term culture, which may enhance the therapeutic potential of hiPSC-CMs.


Assuntos
Células-Tronco Pluripotentes Induzidas , Miócitos Cardíacos , Animais , Humanos , Ratos , Western Blotting , Diferenciação Celular , Movimento Celular
18.
Biochem Biophys Res Commun ; 425(2): 244-9, 2012 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-22828505

RESUMO

Agents that target the activity of the mammalian target of rapamycin (mTOR) kinase in humans are associated with proteinuria. However, the mechanisms underlying mTOR activity and signaling within the kidney are poorly understood. In this study, we developed a sensitive immunofluorescence technique for the evaluation of activated pmTOR and its associated signals in situ. While we find that pmTOR is rarely expressed in normal non-renal tissues, we consistently find intense expression in glomeruli within normal mouse and human kidneys. Using double staining, we find that the expression of pmTOR co-localizes with nephrin in podocytes and expression appears minimal within other cell types in the glomerulus. In addition, we found that pmTOR was expressed on occasional renal tubular cells within mouse and human kidney specimens. We also evaluated mTOR signaling in magnetic bead-isolated glomeruli from normal mice and, by Western blot analysis, we confirmed function of the pathway in glomerular cells vs. interstitial cells. Furthermore, we found that the activity of the pathway as well as the expression of VEGF, a target of mTOR-induced signaling, were reduced within glomeruli of mice following treatment with rapamycin. Collectively, these findings demonstrate that the mTOR signaling pathway is constitutively hyperactive within podocytes. We suggest that pmTOR signaling functions to regulate glomerular homeostasis in part via the inducible expression of VEGF.


Assuntos
Glomérulos Renais/enzimologia , Complexos Multiproteicos/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Imunofluorescência , Homeostase , Humanos , Glomérulos Renais/efeitos dos fármacos , Alvo Mecanístico do Complexo 1 de Rapamicina , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Podócitos/enzimologia , Transdução de Sinais , Sirolimo/farmacologia , Fator A de Crescimento do Endotélio Vascular/biossíntese
19.
Ann Vasc Dis ; 15(4): 344-347, 2022 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-36644265

RESUMO

A 72-year-old man, who was treated 10 years earlier with endovascular aortic aneurysm repair, presented with a fever. Considering the concern of stent graft infection, the patient was treated with antibiotics, but his condition did not improve. He underwent stent graft resection and reconstruction with a Dacron graft. Pathological analysis of the aortic wall and computed tomography revealed recurrent intimal sarcoma, and the patient underwent resurgery. During follow-up, he underwent two additional resections for local recurrence, but he died 17 months later. Our results suggest that intimal sarcoma should be considered during the follow-up after endovascular aortic aneurysm repair.

20.
Medicine (Baltimore) ; 100(31): e26819, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397842

RESUMO

ABSTRACT: Recently, activities of daily living (ADL) were identified as a prognostic factor among elderly patients with heart disease; however, a specific association between ADL and prognosis after cardiac and aortic surgery is not well established. We aimed to clarify the impact of ADL capacity at discharge on prognosis in elderly patients after cardiac and aortic surgery.This retrospective cohort study included 171 elderly patients who underwent open operation for cardiovascular disease in a single center (median age: 74 years; men: 70%). We used the Barthel Index (BI) as an indicator for ADL. Patients were classified into 2 groups according to the BI at discharge, indicating a high (BI ≥ 85) or low (BI < 85) ADL status. All-cause mortality and unplanned readmission events were observed after discharge.Thirteen all-cause mortality and 44 all-cause unplanned readmission events occurred during the median follow-up of 365 days. Using Kaplan-Meier analysis, a low ADL status was determined to be significantly associated with all-cause mortality and unplanned readmission. In the multivariable Cox proportional hazard models, a low ADL status was an independent predictor of all-cause mortality and unplanned readmission after adjusting for age, sex, length of hospital stay, and other variables (including preoperative status, surgical parameter, and postoperative course).A low ADL status at discharge predicted all-cause mortality and unplanned readmission in elderly patients after cardiac and aortic surgery. A comprehensive approach from the time of admission to postdischarge to improve ADL capacity in elderly patients undergoing cardiac and aortic surgery may improve patient outcomes.


Assuntos
Atividades Cotidianas , Procedimentos Cirúrgicos Cardiovasculares , Alta do Paciente , Readmissão do Paciente/estatística & dados numéricos , Assistência ao Convalescente/métodos , Assistência ao Convalescente/organização & administração , Idoso , Doenças Cardiovasculares/cirurgia , Procedimentos Cirúrgicos Cardiovasculares/efeitos adversos , Procedimentos Cirúrgicos Cardiovasculares/métodos , Procedimentos Cirúrgicos Cardiovasculares/mortalidade , Feminino , Humanos , Japão/epidemiologia , Estimativa de Kaplan-Meier , Tempo de Internação/estatística & dados numéricos , Masculino , Desempenho Físico Funcional , Prognóstico , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco
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