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1.
Medicina (Kaunas) ; 57(4)2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33804963

RESUMO

Background: Establishing the diagnosis of COVID-19 and Pneumocystisjirovecii pulmonary coinfection is difficult due to clinical and radiological similarities that exist between the two disorders. For the moment, fungal coinfections are underestimated in COVID-19 patients. Case presentation: We report the case of a 52-year-old male patient, who presented to the emergency department for severe dyspnea and died 17 h later. The RT-PCR test performed at his admission was negative for SARS-CoV-2. Retesting of lung fragments collected during autopsy revealed a positive result for SARS-CoV-2. Histopathological examination showed preexisting lesions, due to comorbidities, as well as recent lesions: massive lung thromboses, alveolar exudate rich in foam cells, suprapleural and intra-alveolar Pneumocystisjirovecii cystic forms, and bilateral adrenal hemorrhage. Conclusion: COVID-19 and P.jirovecii coinfection should be considered, particularly in critically ill patients, and we recommend the systematic search for P. jirovecii in respiratory samples.


Assuntos
/patologia , Pulmão/patologia , Pneumonia por Pneumocystis/patologia , Insuficiência Respiratória/patologia , Trombose/patologia , Lesão Renal Aguda/complicações , Insuficiência Hepática Crônica Agudizada/complicações , Doenças das Glândulas Suprarrenais/complicações , Doenças das Glândulas Suprarrenais/patologia , Autopsia , Coinfecção/patologia , Exsudatos e Transudatos , Evolução Fatal , Fibrose , Células Espumosas/patologia , Hemorragia/complicações , Hemorragia/patologia , Humanos , Hipertensão/complicações , Hepatopatias Alcoólicas/complicações , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Pneumonia por Pneumocystis/complicações , Artéria Pulmonar/patologia , Veias Pulmonares/patologia , Insuficiência Respiratória/etiologia , Trombose/etiologia
2.
Int J Mol Sci ; 22(6)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33803922

RESUMO

Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by a sustained elevation of pulmonary artery (PA) pressure, right ventricular failure, and premature death. Enhanced proliferation and resistance to apoptosis (as seen in cancer cells) of PA smooth muscle cells (PASMCs) is a major pathological hallmark contributing to pulmonary vascular remodeling in PAH, for which current therapies have only limited effects. Emerging evidence points toward a critical role for Enhancer of Zeste Homolog 2 (EZH2) in cancer cell proliferation and survival. However, its role in PAH remains largely unknown. The aim of this study was to determine whether EZH2 represents a new factor critically involved in the abnormal phenotype of PAH-PASMCs. We found that EZH2 is overexpressed in human lung tissues and isolated PASMCs from PAH patients compared to controls as well as in two animal models mimicking the disease. Through loss- and gain-of-function approaches, we showed that EZH2 promotes PAH-PASMC proliferation and survival. By combining quantitative transcriptomic and proteomic approaches in PAH-PASMCs subjected or not to EZH2 knockdown, we found that inhibition of EZH2 downregulates many factors involved in cell-cycle progression, including E2F targets, and contributes to maintain energy production. Notably, we found that EZH2 promotes expression of several nuclear-encoded components of the mitochondrial translation machinery and tricarboxylic acid cycle genes. Overall, this study provides evidence that, by overexpressing EZH2, PAH-PASMCs remove the physiological breaks that normally restrain their proliferation and susceptibility to apoptosis and suggests that EZH2 or downstream factors may serve as therapeutic targets to combat pulmonary vascular remodeling.


Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteoma/genética , Hipertensão Arterial Pulmonar/genética , Transcriptoma/genética , Animais , Apoptose/genética , Proliferação de Células/genética , Ciclo do Ácido Cítrico/genética , Epigênese Genética/genética , Feminino , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Humanos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Hipertensão Arterial Pulmonar/patologia , Artéria Pulmonar/crescimento & desenvolvimento , Artéria Pulmonar/patologia , Ratos
3.
Biomed Res Int ; 2021: 8851736, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33778084

RESUMO

Purpose: This study is aimed at assessing the prevalence of pulmonary artery filling defects (PAFDs) consistent with pulmonary artery embolism (PAE) in patients with SARS-CoV-2 infection and at investigating possible radiological or clinical predictors. Materials and Methods: Computed Tomography Pulmonary Angiographies (CTPAs) from 43 consecutive patients with a confirmed COVID-19 infection were retrospectively reviewed, taking into consideration the revised Geneva score and the D-dimer value for each patient. Filling defects within the pulmonary arteries were recorded along with pleural and parenchymal findings such as ground glass opacities, consolidation, crazy paving, linear consolidation, and pleural effusion. All these variables were compared between patients with and without PAFD. The predictive performance of statistically different parameters was investigated using the receiver operating characteristics (ROC). Results: Pulmonary embolism was diagnosed in 15/43 patients (35%), whereas CTPA and parenchymal changes related to pulmonary COVID-19 disease were evident in 39/43 patients (91%). The revised Geneva score and the mean D-dimer value obtained using two consecutive measurements were significantly higher in patients with PAFD. The ROC analysis demonstrated that a mean D-dimer value is the parameter with the higher predictivity (AUC 0.831) that is a cut-off value > 1800 µg/l which predicts the probability of PAFD with a sensitivity and specificity of 70% and 78%, respectively. Conclusions: This single centre retrospective report shows a high prevalence of pulmonary artery filling defects revealed using CTPA in COVID-19 patients and demonstrates that the mean value of multiple D-dimer measurements may represent a predicting factor of this complication.


Assuntos
/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/métodos , Artéria Pulmonar/diagnóstico por imagem , Adulto , Idoso , /virologia , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Prevalência , Artéria Pulmonar/patologia , Artéria Pulmonar/virologia , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/virologia , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade
4.
Adv Exp Med Biol ; 1303: 13-32, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33788185

RESUMO

Pulmonary Arterial Hypertension (PAH) is a progressive vascular disease arising from the narrowing of pulmonary arteries (PA) resulting in high pulmonary arterial blood pressure and ultimately right ventricular (RV) failure. A defining characteristic of PAH is the excessive remodeling of PA that includes increased proliferation, inflammation, and fibrosis. There is no cure for PAH nor interventions that effectively impede or reverse PA remodeling, and research over the past several decades has sought to identify novel molecular mechanisms of therapeutic benefit. Galectin-3 (Gal-3; Mac-2) is a carbohydrate-binding lectin that is remarkable for its chimeric structure, comprised of an N-terminal oligomerization domain and a C-terminal carbohydrate-recognition domain. Gal-3 is a regulator of changes in cell behavior that contribute to aberrant PA remodeling including cell proliferation, inflammation, and fibrosis, but its role in PAH is poorly understood. Herein, we summarize the recent literature on the role of Gal-3 in the development of PAH and provide experimental evidence supporting the ability of Gal-3 to influence reactive oxygen species (ROS) production, NOX enzyme expression, inflammation, and fibrosis, which contributes to PA remodeling. Finally, we address the clinical significance of Gal-3 as a target in the development of therapeutic agents as a treatment for PAH.


Assuntos
Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Animais , Modelos Animais de Doenças , Fibrose , Galectina 3/genética , Inflamação/patologia , Artéria Pulmonar/patologia , Espécies Reativas de Oxigênio , Remodelação Vascular
5.
Life Sci ; 274: 119366, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33741419

RESUMO

AIMS: N6-methyladenosine (m6A) is the most prevalent internal chemical RNA modification in mammal mRNAs. Accumulating evidence has shown the critical role of m6A in cardiovascular diseases including cardiac hypertrophy, heart failure, ischemic heart disease, vascular calcification, restenosis, and aortic aneurysm. However, whether m6A participates in the occurrence and development of hypoxic pulmonary hypertension (HPH) remains largely unknown. The present study aims to explore the role of key transferase METTL3, in the development of HPH. MATERIALS AND METHODS: Pulmonary artery smooth muscle cells (PASMCs) and hypoxic rat models were used to research the METTL3-mediated m6A in HPH. EdU, transwell and TUNEL were performed to evaluate the proliferation, migration and apoptosis rates. m6A RNA Methylation Quantification Kit and m6A-qPCR were utilized to measure the total m6A level and m6A level of PTEN mRNA. RNA immunoprecipitation was used to detect the interaction between METTL3 and PTEN mRNA. KEY FINDINGS: Both METTL3 mRNA and protein were found abnormally upregulated in vivo and in vitro. Furthermore, downregulation of METTL3 attenuated PASMCs proliferation and migration. In addition, m6A binding protein YTHDF2 was found significantly increased in PASMCs under hypoxia. YTHDF2 recognized METTL3 mediated m6A modified PTEN mRNA and promoted the degradation of PTEN. Decreased PTEN led to over-proliferation of PASMCs through activation of PI3K/Akt signaling pathway. SIGNIFICANCE: METTL3/YTHDF2/PTEN axis exerts a significant role in hypoxia induced PASMCs proliferation, providing a novel therapeutic target for HPH.


Assuntos
Adenosina/análogos & derivados , Hipóxia/fisiopatologia , Metiltransferases/metabolismo , Miócitos de Músculo Liso/patologia , Hipertensão Arterial Pulmonar/patologia , Artéria Pulmonar/patologia , RNA Mensageiro/metabolismo , Adenosina/química , Animais , Apoptose , Proliferação de Células , Masculino , Metilação , Metiltransferases/genética , Miócitos de Músculo Liso/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Hipertensão Arterial Pulmonar/metabolismo , Artéria Pulmonar/metabolismo , RNA Mensageiro/química , RNA Mensageiro/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
6.
Mol Med Rep ; 23(3)2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33495839

RESUMO

The aim of the present study was to explore the effect of microRNA (miR)­153 on the proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) in a hypoxic condition by targeting ρ­associated, coiled­coil­containing protein kinase 1 (ROCK1) and nuclear factor of activated T cells cytoplasmic 3 (NFATc3). The right ventricular systolic pressure, right ventricular hypertrophy index, medial wall thickness and medial wall area were studied at different time­points after rats were exposed to hypoxia. Western blot analysis was used to detect ROCK1 and NFATc3 protein levels. In addition, reverse transcription­quantitative (RT­q) PCR was performed to confirm the mRNA levels of miR­153, ROCK1 and NFATc3 in human (H)PASMCs under hypoxic conditions. Transfected cells were then used to evaluate the effect of miR­153 on cell proliferation and migration abilities. The association between miR­153 and ROCK1 or NFATc3 was identified through double luciferase assays. Hypoxia induced pulmonary vascular remodeling and pulmonary arterial hypertension, which resulted from the abnormal proliferation of HPASMCs. ROCK1 and NFATc3 were the target genes of miR­153 and miR­153 mimic inhibited the protein expressions of ROCK1 and NFATc3 in HPASMCs and further inhibited cell proliferation and migration under hypoxic conditions. By contrast, the miR­153 inhibitor promoted the proliferation and migration of HPASMCs. miR­153 regulated the proliferation and migration of HPASMCs under hypoxia by targeting ROCK1 and NFATc3.


Assuntos
Movimento Celular , Proliferação de Células , MicroRNAs/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Fatores de Transcrição NFATC/metabolismo , Artéria Pulmonar/metabolismo , Quinases Associadas a rho/metabolismo , Animais , Hipóxia Celular , Masculino , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Artéria Pulmonar/patologia , Ratos , Ratos Sprague-Dawley
8.
Mol Med Rep ; 23(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33236156

RESUMO

The Notch signaling pathway participates in pulmonary artery smooth muscle cell (PASMC) proliferation and apoptosis. Astragaloside IV (AS­IV) is an effective antiproliferative treatment for vascular diseases. The present study aimed to investigate the protective effects and mechanisms underlying AS­IV on hypoxia­induced PASMC proliferation and pulmonary vascular remodeling in pulmonary arterial hypertension (PAH) model rats. Rats were divided into the following four groups: i) normoxia; ii) hypoxia (10% O2); iii) treatment, hypoxia + intragastrical administration of AS­IV (2 mg/kg) daily for 28 days; and iv) DAPT, hypoxia + AS­IV treatment + subcutaneous administration of DAPT (10 mg/kg) three times daily. The effects of AS­IV treatment on the development of hypoxia­induced PAH, right ventricle (RV) hypertrophy and pulmonary vascular remodeling were examined. Furthermore, PASMCs were treated with 20 µmol/l AS­IV under hypoxic conditions for 48 h. To determine the effect of Notch signaling in vascular remodeling and the potential mechanisms underlying AS­IV treatment, 5 mmol/l γ­secretase inhibitor [N­[N­(3,5­difluorophenacetyl)­L­alanyl]­S­phenylglycine t­butyl ester (DAPT)] was used. Cell viability and apoptosis were determined by performing the MTT assay and flow cytometry, respectively. Immunohistochemistry was conducted to detect the expression of proliferating cell nuclear antigen (PCNA). Moreover, the mRNA and protein expression levels of Notch­3, Jagged­1, hes family bHLH transcription factor 5 (Hes­5) and PCNA were measured via reverse transcription­quantitative PCR and western blotting, respectively. Compared with the normoxic group, hypoxia­induced PAH model rats displayed characteristics of PAH and RV hypertrophy, whereas AS­IV treatment alleviated PAH and prevented RV hypertrophy. AS­IV also inhibited hypoxia­induced pulmonary vascular remodeling, as indicated by reduced wall thickness and increased lumen diameter of pulmonary arterioles, and decreased muscularization of distal pulmonary vasculature in hypoxia­induced PAH model rats. Compared with normoxia, hypoxia promoted PASMC proliferation in vitro, whereas AS­IV treatment inhibited hypoxia­induced PASMC proliferation by downregulating PCNA expression in vitro and in vivo. In hypoxia­treated PAH model rats and cultured PASMCs, AS­IV treatment reduced the expression levels of Jagged­1, Notch­3 and Hes­5. Furthermore, Notch signaling inhibition via DAPT significantly inhibited the pulmonary vascular remodeling effect of AS­IV in vitro and in vivo. Collectively, the results indicated that AS­IV effectively reversed hypoxia­induced pulmonary vascular remodeling and PASMC proliferation via the Notch signaling pathway. Therefore, the present study provided novel insights into the mechanism underlying the use of AS­IV for treatment of vascular diseases, such as PAH.


Assuntos
Hipóxia/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Artéria Pulmonar/metabolismo , Receptores Notch/metabolismo , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Triterpenos/farmacologia , Remodelação Vascular/efeitos dos fármacos , Animais , Hipóxia/patologia , Masculino , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Artéria Pulmonar/patologia , Ratos , Ratos Sprague-Dawley
9.
Cardiovasc Pathol ; 50: 107270, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32858207

RESUMO

We report a case of inflammatory myofibroblastic tumor affecting the pulmonary artery in a 15-year-old male, presenting with a clinical scenario of recurrent pulmonary embolisms. During diagnostic workup for persistent fever, a mass in main pulmonary artery was detected at echocardiography and confirmed at angio-CT scan. The patient underwent a first successful surgical resection and discharged home with no echocardiographic evidence of residual lesions, but, after 5 months, he was admitted for hemoptysis and an angio CT-scan showed a mass in right pulmonary artery with multiple distal perfusion defects, suspicious for both thrombotic and secondary lesions. To prevent further embolisms, the patient was scheduled for a second surgical procedure, which allowed a complete removal of the tumor from major branches of right pulmonary arteries. Our experience highlights that, despite of its intermediate malignancy, inflammatory myofibroblastic tumor may behave as an extremely dangerous condition, requiring multiple surgeries an integrated and multidisciplinary approach.


Assuntos
Granuloma de Células Plasmáticas Pulmonar/complicações , Artéria Pulmonar , Embolia Pulmonar/etiologia , Adolescente , Humanos , Masculino , Granuloma de Células Plasmáticas Pulmonar/diagnóstico , Granuloma de Células Plasmáticas Pulmonar/cirurgia , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/patologia , Artéria Pulmonar/cirurgia , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/prevenção & controle , Recidiva , Resultado do Tratamento
10.
Eur J Radiol ; 134: 109442, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33321459

RESUMO

PURPOSE: The vascular enlargement (VE) pattern differs from previously described imaging patterns for pneumonia. This study aimed to investigate the incidence, computed tomography (CT) characteristics, and diagnostic value of the VE pattern in coronavirus disease 2019 (COVID-19). METHOD: The CT data of 106 patients with COVID-19 from January 19 to February 29, 2020, and 52 patients with influenza virus pneumonia (IVP) from January 2018 to February 2020 were retrospectively collected. The incidences of the VE pattern between the two groups were compared. The CT manifestations of COVID-19 were analyzed with a particular focus on the VE pattern's specific CT signs, dynamic changes, and relationships with lesion size and disease severity. RESULTS: Peripheral and multilobar ground-glass opacities (GGOs) or mixed GGOs with various sizes and morphologies were typical features of COVID-19 on initial CT. The VE pattern was more common in COVID-19 (88/106, 83.02 %) than in IVP (10/52, 19.23 %) on initial CT (P < 0.001). Three special VE-pattern-specific CT signs, including central vascular sign, ginkgo leaf sign, and comb sign, were identified. Four types of dynamic changes in the VE pattern were observed on initial and follow-up CT, which were closely associated with the evolution of lesions and the time interval from the onset of symptoms to initial CT scan. The VE pattern in COVID-19 was more commonly seen in larger lesions and patients with severe-critical type (all P < 0.001). CONCLUSIONS: The VE pattern is a valuable CT sign for differentiating COVID-19 from IVP, which correlates with more extensive or serious disease. A good understanding of the CT characteristics of the VE pattern may contribute to the early and accurate diagnosis of COVID-19 and prediction of the evolution of lesions.


Assuntos
/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Pneumonia/diagnóstico por imagem , Artéria Pulmonar/patologia , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/patologia , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Diagnóstico Diferencial , Feminino , Humanos , Influenza Humana/diagnóstico por imagem , Influenza Humana/patologia , Pulmão/irrigação sanguínea , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Pneumonia/patologia , Artéria Pulmonar/diagnóstico por imagem , Estudos Retrospectivos , Adulto Jovem
11.
Biomed Pharmacother ; 133: 111056, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378960

RESUMO

Pulmonary arterial hypertension (PAH) is a progressive and lethal cardiopulmonary. Pulmonary vascular remodeling (PVR) caused by excessive proliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs) is the chief pathological feature of PAH. Dioscin is a natural product that possesses multiple pharmacological activities, but its effect on PAH remains unclear. In this study, effect of dioscin on vascular remodeling in PAH was assessed in hypoxia-induced PASMCs, hypoxia-induced and monocrotaline (MCT)-induced rats. Western blot, Real-time PCR and siRNA transfection tests were applied to evaluate the possible mechanisms of dioscin. In vitro experiments, results showed dioscin markedly inhibited the proliferation and migration, and promoted apoptosis of hypoxic PASMCs. In vivo, dioscin significantly decreased the right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI), and improved pulmonary vascular stenosis in rats induced by hypoxia or MCT. Molecular mechanism studies showed that dioscin significantly reduced the expression of growth factor receptor-bound protein 2 (GRB2). Subsequently, dioscin reduced the expressions of Ras, Cyclin D1, CDK4, c-Fos, PCNA and p-ERK to inhibit proliferation and migration of PASMCs, inhibited p-PI3K and p-AKT levels and increased Bax/Bcl2 ratio to promote cell apoptosis. GRB2 siRNA transfection in PASMCs further confirmed that the inhibitory action of dioscin in PAH was evoked by adjusting GRB2/ERK/PI3K-AKT signal. Taken together, our study indicated that dioscin attenuates PAH through adjusting GRB2/ERK/PI3K-AKT signal to inhibit PASMCs proliferation and migration, and promote apoptosis, and dioscin may be developed as a therapeutic strategy for treating PAH in the future.


Assuntos
Diosgenina/análogos & derivados , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteína Adaptadora GRB2/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Hipertensão Arterial Pulmonar/tratamento farmacológico , Remodelação Vascular/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Diosgenina/farmacologia , Modelos Animais de Doenças , Proteína Adaptadora GRB2/genética , Masculino , Músculo Liso Vascular/enzimologia , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/enzimologia , Miócitos de Músculo Liso/patologia , Fosforilação , Hipertensão Arterial Pulmonar/enzimologia , Hipertensão Arterial Pulmonar/patologia , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/enzimologia , Artéria Pulmonar/patologia , Ratos Sprague-Dawley , Transdução de Sinais
12.
Biomed Pharmacother ; 133: 111081, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378977

RESUMO

OBJECTIVE: A growing evidence demonstrates that inflammation is a major contributor to the pathogenesis of pulmonary arterial hypertension (PAH). However, blocking inflammation has only been shown to be of minor clinical benefit due to a lack of understanding of the precise inflammation present in PAH. Thus, the present study aimed to investigate characteristics of inflammatory process in PAH induced by monocrotaline (MCT) in rats. METHODS: Adult male Sprague-Dawley rats received a single dose of MCT (50 mg/kg, ip), and the occurrence of PAH and inflammation biomarkers were measured at 3, 6, 9, 12, 15, 18, 21, 24, 27 and 30 days after MCT injection. RESULTS: From the 6th day after the injection of MCT, the mean pulmonary artery pressure gradually increased and doubled on the 30th day, accompanied by right ventricular hypertrophy and pulmonary arterial remodeling in a time-dependent manner. In the first 6 days after MCT treatment, only pro-inflammatory cytokines TNF-α, IL-1ß increased, which was defined as acute inflammatory phase, after that, both pro-inflammatory factors TNF-α, IL-1ß, IL-6, IL-12 and anti-inflammatory factors Arg1, IL-10, TGF-ß increased, which was defined as chronic inflammatory phase. The M1/M2 macrophage ratios in lung and alveolar lavage fluid were elevated on the 6th and 30th day, moreover, which were higher on the 6th than 30th day, and the PI3K/Akt signaling pathway increased along with the progression of PAH and correlated with pro-inflammatory proteins, which revealed also to some extent the characteristics of inflammation of PAH induced by MCT. CONCLUSION: The course of PAH induced by MCT injection is progressive with persistent inflammation, which is defined as acute inflammatory phase within 6 days after MCT treatment, after that, is defined as chronic inflammatory phase.


Assuntos
Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Inflamação/metabolismo , Hipertensão Arterial Pulmonar/metabolismo , Artéria Pulmonar/metabolismo , Remodelação Vascular , Animais , Pressão Arterial , Citocinas/genética , Modelos Animais de Doenças , Hipertrofia Ventricular Direita/induzido quimicamente , Hipertrofia Ventricular Direita/metabolismo , Hipertrofia Ventricular Direita/fisiopatologia , Inflamação/induzido quimicamente , Inflamação/patologia , Inflamação/fisiopatologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Monocrotalina , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Hipertensão Arterial Pulmonar/induzido quimicamente , Hipertensão Arterial Pulmonar/patologia , Hipertensão Arterial Pulmonar/fisiopatologia , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiopatologia , Ratos Sprague-Dawley , Transdução de Sinais , Fatores de Tempo
13.
J Card Surg ; 35(10): 2802-2803, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33043656

RESUMO

We present the clinical case of a 60-year-old woman complained of dyspnea on exertion. Echocardiogram showed a giant mass in the right ventricle (RV) with obstruction to the outflow tract. Thorax computed tomography confirmed a mass of greater than 60 mm infiltrating RV and causing severe stenosis in the pulmonary artery, with severe pericardial effusion. Cardiac surgery was performed for tumor resection and pulmonary root replacement with a biological valved conduit. Histological analysis diagnosed a poorly differentiated large-cell neuroendocrine carcinoma. The patient had no immediate postoperative complications and has completed radiotherapy at a 9-month follow-up.


Assuntos
Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Neuroendócrino/cirurgia , Procedimentos Cirúrgicos Cardíacos/métodos , Ecocardiografia , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasias Cardíacas/cirurgia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/cirurgia , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/cirurgia , Tomografia Computadorizada por Raios X , Implante de Prótese Vascular/métodos , Carcinoma Neuroendócrino/complicações , Carcinoma Neuroendócrino/patologia , Constrição Patológica/diagnóstico por imagem , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Feminino , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/patologia , Ventrículos do Coração/patologia , Humanos , Pessoa de Meia-Idade , Derrame Pericárdico/diagnóstico por imagem , Derrame Pericárdico/etiologia , Artéria Pulmonar/patologia , Índice de Gravidade de Doença , Resultado do Tratamento
14.
PLoS One ; 15(10): e0240078, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33017451

RESUMO

BACKGROUND: To evaluate chest-computed-tomography (CT) scans in coronavirus-disease-2019 (COVID-19) patients for signs of organizing pneumonia (OP) and microinfarction as surrogate for microscopic thromboembolic events. METHODS: Real-time polymerase-chain-reaction (RT-PCR)-confirmed COVID-19 patients undergoing chest-CT (non-enhanced, enhanced, pulmonary-angiography [CT-PA]) from March-April 2020 were retrospectively included (COVID-19-cohort). As control-groups served 175 patients from 2020 (cohort-2020) and 157 patients from 2019 (cohort-2019) undergoing CT-PA for pulmonary embolism (PE) during the respective time frame at our institution. Two independent readers assessed for presence and location of PE in all three cohorts. In COVID-19 patients additionally parenchymal changes typical of COVID-19 pneumonia, infarct pneumonia and OP were assessed. Inter-reader agreement and prevalence of PE in different cohorts were calculated. RESULTS: From 68 COVID-19 patients (42 female [61.8%], median age 59 years [range 32-89]) undergoing chest-CT 38 obtained CT-PA. Inter-reader-agreement was good (k = 0.781). On CT-PA, 13.2% of COVID-19 patients presented with PE whereas in the control-groups prevalence of PE was 9.1% and 8.9%, respectively (p = 0.452). Up to 50% of COVID-19 patients showed changes typical for OP. 21.1% of COVID-19 patients suspected with PE showed subpleural wedge-shaped consolidation resembling infarct pneumonia, while only 13.2% showed visible filling defects of the pulmonary artery branches on CT-PA. CONCLUSION: Despite the reported hypercoagulability in critically ill patients with COVID-19, we did not encounter higher prevalence of PE in our patient cohort compared to the control cohorts. However, patients with suspected PE showed a higher prevalence of lung changes, resembling patterns of infarct pneumonia or OP and CT-signs of pulmonary-artery hypertension.


Assuntos
Infecções por Coronavirus/patologia , Pneumonia Viral/patologia , Artéria Pulmonar/patologia , Infarto Pulmonar/diagnóstico por imagem , Tromboembolia/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/diagnóstico por imagem , Feminino , Humanos , Pulmão/irrigação sanguínea , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
15.
PLoS One ; 15(10): e0239561, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33091038

RESUMO

Pulmonary hypertension and cor pulmonale are complications of severe equine asthma, as a consequence of pulmonary hypoxic vasoconstriction. However, as pulmonary hypertension is only partially reversible by oxygen administration, other etiological factors are likely involved. In human chronic obstructive pulmonary disease, pulmonary artery remodeling contributes to the development of pulmonary hypertension. In rodent models, pulmonary vascular remodeling is present as a consequence of allergic airway inflammation. The present study investigated the presence of remodeling of the pulmonary arteries in severe equine asthma, its distribution throughout the lungs, and its reversibility following long-term antigen avoidance strategies and inhaled corticosteroid administration. Using histomorphometry, the total wall area of pulmonary arteries from different regions of the lungs of asthmatic horses and controls was measured. The smooth muscle mass of pulmonary arteries was also estimated on lung sections stained for α-smooth muscle actin. Reversibility of vascular changes in asthmatic horses was assessed after 1 year of antigen avoidance alone or treatment with inhaled fluticasone. Pulmonary arteries showed increased wall area in apical and caudodorsal lung regions of asthmatic horses in both exacerbation and remission. The pulmonary arteries smooth muscle mass was similarly increased. Both treatments reversed the increase in wall area. However, a trend for normalization of the vascular smooth muscle mass was observed only after treatment with antigen avoidance, but not with fluticasone. In conclusion, severe equine asthma is associated with remodeling of the pulmonary arteries consisting in an increased smooth muscle mass. The resulting narrowing of the artery lumen could enhance hypoxic vasoconstriction, contributing to pulmonary hypertension. In our study population, the antigen avoidance strategy appeared more promising than inhaled corticosteroids in controlling vascular remodeling. However, further studies are needed to support the reversibility of vascular smooth muscle mass remodeling after asthma treatment.


Assuntos
Asma/patologia , Asma/fisiopatologia , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiopatologia , Remodelação Vascular , Animais , Cavalos
16.
Anticancer Res ; 40(10): 5837-5844, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988913

RESUMO

BACKGROUND/AIM: Renal cell carcinoma (RCC) is one of the most common malignancies of the urinary tract. Venous migration, tumor thrombus and metastases are often seen in patients with RCC and are adverse prognostic factors. Intravascular tumor growth along the renal vein into the inferior vena cava occurs in up to 10% of all patients with RCC. Furthermore, extension of the tumor reaching the right atrium is detected in approximately 1% of all patients. Synchronous involvement of pulmonary arteries with tumor emboli is very rare and challenging. Management of metastatic RCC includes surgical resection of renal and metastatic lesions. We present 3 cases of patients with RCC tumor thrombus extending into the inferior vena cava (IVC) and with pulmonary emboli of the tumor thrombus into one of the branches of the main pulmonary artery. All the cases had simultaneous resection of the kidney tumor with the tumor thrombus and pulmonary lobectomy that included the tumor emboli with satisfactory outcome. CASE REPORT: We present a series of cases of RCC with tumor extension into the inferior vena cava (IVC) and with tumor emboli to the pulmonary arteries. Surgical procedure in all cases consisted of radical nephrectomy with IVC tumor thrombus resection, along with a thoracotomy with lung resection including the tumor emboli to one of the branches of the main pulmonary artery. Synchronous metastatic lesions were found on the liver in one case and contiguous extension of renal tumor to the pancreas in another. CONCLUSION: In patients with IVC thrombus with synchronous pulmonary artery tumor embolus, such as the cases presented in this series, a careful multidisciplinary management approach is preferable. Transplant technique used in our open approach minimizes complications, blood loss, and provides excellent visualization for abdominal vascular manipulation of IVC. This provides a potentially curable treatment option with acceptable survival rates.


Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Pulmonares/cirurgia , Artéria Pulmonar/cirurgia , Veia Cava Inferior/cirurgia , Adulto , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/patologia , Feminino , Humanos , Rim/diagnóstico por imagem , Rim/patologia , Rim/cirurgia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Metástase Neoplásica , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Nefrectomia/métodos , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/patologia , Veias Renais/diagnóstico por imagem , Veias Renais/patologia , Veias Renais/cirurgia , Trombose/diagnóstico por imagem , Trombose/patologia , Trombose/cirurgia , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/patologia , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/patologia , Trombose Venosa/cirurgia
17.
Semin Thromb Hemost ; 46(7): 850-852, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32886934
18.
Leg Med (Tokyo) ; 47: 101774, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32777694

RESUMO

Radiotherapy, one of the standard therapies for lung cancer management, may cause severe late complications. In this case report, we describe the forensic autopsy report of a middle-aged man who died from a massive hemoptysis due to a bronchus-pulmonary artery fistula that developed 19 years after radiotherapy. The man, in his 50 s, suddenly developed hemoptysis at home and collapsed. He was in complete remission with no signs of recurrence. Autopsy revealed massive hemorrhage from the bronchus-pulmonary artery fistula, where radiotherapy had been focused. Histopathological findings showed chondronecrosis of the bronchus, disruption of elastic fibers of the pulmonary artery, and marked thickening of the intima of the small arteries around the fistula, which were compatible with radiation reaction. Neither cancer recurrence nor infection was evident. This case suggests that a late complication of radiotherapy should be considered in the differential diagnosis of a patient who was previously received radiotherapy and presents with massive hemoptysis. In such cases, a detailed history on previous therapies and careful examination of the origin of hemorrhage are necessary to determine the cause of death.


Assuntos
Autopsia , Fístula Brônquica/etiologia , Medicina Legal , Neoplasias Pulmonares/radioterapia , Artéria Pulmonar , Radioterapia/efeitos adversos , Fístula Vascular/etiologia , Fístula Brônquica/diagnóstico , Fístula Brônquica/patologia , Diagnóstico Diferencial , Evolução Fatal , Hemoptise/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/patologia , Índice de Gravidade de Doença , Fatores de Tempo , Fístula Vascular/diagnóstico , Fístula Vascular/patologia
19.
Cardiovasc Pathol ; 49: 107263, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32784110

RESUMO

Since its recognition in December 2019, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has rapidly spread globally causing a pandemic that represents the greatest medical challenge in decades. The aim of the study was to evaluate the spectrum of cardiopulmonary pathology of COVID-19 based on (non-minimal invasive) autopsies performed on 14 COVID-19 decedents. Bilateral diffuse alveolar damage (DAD) was found in all patients. Superimposed acute bronchopneumonia was present in 11 of 14 (78.6%) patients and was considered the major cause of death in 2 patients. A key finding was the presence of thrombotic/thromboembolic vascular occlusions. We classified 5 types of pulmonary thrombi: 1. capillary microthrombi (11/14, 78.6%); 2. partially organized thrombi in mid-sized pulmonary arteries with complete vessel occlusion; 3. non-organized thrombi in mid-sized pulmonary arteries that did not completely fill out the vessel lumen and probably represented thromboemboli rather than thrombosis; 4. bone marrow emboli (1/14, 7.1%); and 5. septic pulmonary thromboemboli (1/14, 7.1%). Pulmonary thrombi in mid-sized arteries were noted in 5 of 14 (35.7%) patients, causing pulmonary infarction and/or pulmonary hemorrhage. All patients had evidence of chronic cardiac disease, including myocardial hypertrophy (13/14, 92.9%), mild to marked coronary artery atherosclerosis (14/14, 100%) and focal myocardial fibrosis (3/14, 21.4%). Acute myocardial infarction was found as concurrent cause of death in 3 (21.4%) patients, and significant cardiac hypertrophy (heart weight 750 g) was present in 1 (7.1%) patient with ATTR-positive cardiac amyloidosis. The autopsy findings confirm that COVID-19 is a systemic disease, with major involvement of the lungs, that increases the risk of cardiac and vascular complications including acute myocardial injury and thrombotic/thromboembolic events. Secondary acute bronchopneumonia is a common complication in patients with COVID-19 and may be the major cause of death.


Assuntos
Broncopneumonia/patologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Artéria Pulmonar/patologia , Trombose/patologia , Idoso , Idoso de 80 Anos ou mais , Autopsia , Betacoronavirus , Broncopneumonia/virologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Pandemias , Embolia Pulmonar/patologia , Embolia Pulmonar/virologia , Trombose/virologia
20.
Ann R Coll Surg Engl ; 102(9): e1-e3, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32735117

RESUMO

This case presents an unusually late complication of oesophagectomy 20-years post-surgery, with upper gastrointestinal bleeding. Further investigation revealed a gastric conduit ulcer eroding into the lower lobe of the right lung, forming a fistula with a basal branch of the right pulmonary artery. Upon successful embolisation, the HydroCoil® was visible on endoscopy. This case highlights the need for lifetime proton pump inhibitor cover post-oesophagectomy and demonstrates that when approaching uncommon presentations of common problems, careful consideration to treatment technique is essential.


Assuntos
Esofagectomia/efeitos adversos , Úlcera Péptica Hemorrágica/etiologia , Artéria Pulmonar , Úlcera Gástrica/etiologia , Idoso , Feminino , Gastroscopia , Humanos , Artéria Pulmonar/patologia , Úlcera Gástrica/diagnóstico
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