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1.
Int J Lab Hematol ; 43 Suppl 1: 29-35, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34288441

RESUMO

Vascular endothelial injury is a hallmark of acute infection at both the microvascular and macrovascular levels. The hallmark of SARS-CoV-2 infection is the current COVID-19 clinical sequelae of the pathophysiologic responses of hypercoagulability and thromboinflammation associated with acute infection. The acute lung injury that initially occurs in COVID-19 results from vascular and endothelial damage from viral injury and pathophysiologic responses that produce the COVID-19-associated coagulopathy. Clinicians should continue to focus on the vascular endothelial injury that occurs and evaluate potential therapeutic interventions that may benefit those with new infections during the current pandemic as they may also be of benefit for future pathogens that generate similar thromboinflammatory responses. The current Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) studies are important projects that will further define our management strategies. At the time of writing this report, two mRNA vaccines are now being distributed and will hopefully have a major impact on slowing the global spread and subsequent thromboinflammatory injury we see clinically in critically ill patients.


Assuntos
COVID-19/complicações , Pandemias , SARS-CoV-2 , Trombofilia/etiologia , Vasculite/etiologia , Anticoagulantes/uso terapêutico , COVID-19/sangue , COVID-19/imunologia , Criança , Coagulação Intravascular Disseminada/etiologia , Endotélio Vascular/lesões , Endotélio Vascular/fisiopatologia , Feminino , Fibrinólise , Previsões , Humanos , Pulmão/irrigação sanguínea , Pulmão/patologia , Gravidez , Complicações Infecciosas na Gravidez/sangue , Tromboembolia/etiologia , Tromboembolia/prevenção & controle
3.
FASEB J ; 35(8): e21679, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34314542

RESUMO

The ability to form a variety of cell-matrix connections is crucial for angiogenesis to take place. Without stable anchorage to the extracellular matrix (ECM), endothelial cells (ECs) are unable to sense, integrate and disseminate growth factor stimulated responses that drive growth of a vascular bed. Neuropilin-2 (NRP2) is a widely expressed membrane-bound multifunctional non-tyrosine kinase receptor, which has previously been implicated in influencing cell adhesion and migration by interacting with α5-integrin and regulating adhesion turnover. α5-integrin, and its ECM ligand fibronectin (FN) are both known to be upregulated during the formation of neo-vasculature. Despite being descriptively annotated as a candidate biomarker for aggressive cancer phenotypes, the EC-specific roles for NRP2 during developmental and pathological angiogenesis remain unexplored. The data reported here support a model whereby NRP2 actively promotes EC adhesion and migration by regulating dynamic cytoskeletal remodeling and by stimulating Rab11-dependent recycling of α5-integrin-p-FAK complexes to newly assembling adhesion sites. Furthermore, temporal depletion of EC-NRP2 in vivo impairs primary tumor growth by disrupting vessel formation. We also demonstrate that EC-NRP2 is required for normal postnatal retinal vascular development, specifically by regulating cell-matrix adhesion. Upon loss of endothelial NRP2, vascular outgrowth from the optic nerve during superficial plexus formation is disrupted, likely due to reduced FAK phosphorylation within sprouting tip cells.


Assuntos
Actinas/metabolismo , Células Endoteliais , Integrina alfa5/metabolismo , Pulmão/irrigação sanguínea , Neovascularização Patológica/metabolismo , Neuropilina-2/fisiologia , Animais , Adesão Celular , Linhagem Celular Tumoral , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Matriz Extracelular/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL
4.
Medicine (Baltimore) ; 100(25): e26483, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160461

RESUMO

ABSTRACT: To investigate the importance of pulmonary vascular measurements on computed tomography (CT) in predicting pulmonary hypertension (PH) and worse outcomes in diffuse cystic lung diseases (DCLDs).We conducted a cross-sectional study of patients with DCLDs. Patients underwent pulmonary function tests, a six-minute walk test (6MWT), chest CT, transthoracic echocardiography, and right heart catheterization. Pulmonary artery (PA) diameter and PA-ascending aorta ratio (PA-Ao ratio) were obtained from CT. Mean pulmonary artery pressure (mPAP) from right heart catheterization was correlated with tomographic, functional, and echocardiographic variables. The association between the PA-Ao ratio with outcomes was determined by Kaplan-Meier curves.Thirty-four patients were included (18 with pulmonary Langerhans cell histiocytosis and 16 with lymphangioleiomyomatosis, mean age 46 ±â€Š9 years). Forced expiratory volume in the first second and lung diffusing capacity for carbon monoxide were 47 ±â€Š20% and 38 ±â€Š21% predicted, respectively. PA diameter and PA-Ao ratio were 29 ±â€Š6 mm and 0.95 ±â€Š0.24, respectively. PA-Ao ratio > 1 occurred in 38.2% of patients. PA-Ao ratio was a good predictor of PH. mPAP correlated best with PA-Ao ratio, PA diameter, oxygen desaturation during six-minute walk test, and echocardiographic variables. Patients with PA-Ao ratio > 1 had greater mPAP, and a higher risk of death or lung transplantation (log-rank, P < .001) than those with PA-Ao ratio ≤ 1.The PA-Ao ratio measured on CT scan has a potential role as a non-invasive tool to predict the presence of PH and as a prognostic parameter in patients with DCLDs.


Assuntos
Aorta/diagnóstico por imagem , Hipertensão Pulmonar/diagnóstico , Pneumopatias/complicações , Transplante de Pulmão/estatística & dados numéricos , Artéria Pulmonar/diagnóstico por imagem , Adulto , Aorta/patologia , Estudos Transversais , Ecocardiografia , Feminino , Humanos , Hipertensão Pulmonar/etiologia , Pulmão/irrigação sanguínea , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pneumopatias/mortalidade , Pneumopatias/patologia , Pneumopatias/cirurgia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Artéria Pulmonar/patologia , Curva ROC , Medição de Risco/estatística & dados numéricos , Tomografia Computadorizada por Raios X , Teste de Caminhada
5.
J Aerosol Med Pulm Drug Deliv ; 34(4): 262-264, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34152840

RESUMO

Despite the various parenchymal presentation of coronavirus disease 2019 (COVID-19) pneumonia, the involvement of the vascular component, the reduction of perfusion in noninjured part of the lung and secondary right to left shunt play an important role in the genesis of the respiratory insufficiency. We present the case of a 72-year-old woman admitted to Livorno Hospital for severe respiratory insufficiency due to SARS-CoV-2 infection unresponsive to noninvasive in whom administration of nebulized phosphodiesterase 3 (PDE3) inhibitor enoximone was able to improve oxygenation avoiding tracheal intubation. Intravenous infusions of phosphodiesterase inhibitors are commonly used as pulmonary vasodilators in the management of pulmonary hypertension. This is the first case showing that inhaled route administration of PDE3 inhibitor enoximone could be important in the management of COVID-19 hypoxemia, to restore perfusion in noninjured part of the lung, improving oxygenation and avoiding risks of systemic infusion.


Assuntos
COVID-19/tratamento farmacológico , Enoximona/administração & dosagem , Hipóxia/tratamento farmacológico , Pulmão/irrigação sanguínea , Inibidores da Fosfodiesterase 3/administração & dosagem , Circulação Pulmonar/efeitos dos fármacos , Administração por Inalação , Aerossóis , Idoso , COVID-19/fisiopatologia , COVID-19/virologia , Feminino , Humanos , Hipóxia/fisiopatologia , Hipóxia/virologia , Nebulizadores e Vaporizadores , Resultado do Tratamento
6.
Crit Care ; 25(1): 186, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074313

RESUMO

BACKGROUND: In acute respiratory distress syndrome (ARDS), extravascular lung water index (EVLWi) and pulmonary vascular permeability index (PVPI) measured by transpulmonary thermodilution reflect the degree of lung injury. Whether EVLWi and PVPI are different between non-COVID-19 ARDS and the ARDS due to COVID-19 has never been reported. We aimed at comparing EVLWi, PVPI, respiratory mechanics and hemodynamics in patients with COVID-19 ARDS vs. ARDS of other origin. METHODS: Between March and October 2020, in an observational study conducted in intensive care units from three university hospitals, 60 patients with COVID-19-related ARDS monitored by transpulmonary thermodilution were compared to the 60 consecutive non-COVID-19 ARDS admitted immediately before the COVID-19 outbreak between December 2018 and February 2020. RESULTS: Driving pressure was similar between patients with COVID-19 and non-COVID-19 ARDS, at baseline as well as during the study period. Compared to patients without COVID-19, those with COVID-19 exhibited higher EVLWi, both at the baseline (17 (14-21) vs. 15 (11-19) mL/kg, respectively, p = 0.03) and at the time of its maximal value (24 (18-27) vs. 21 (15-24) mL/kg, respectively, p = 0.01). Similar results were observed for PVPI. In COVID-19 patients, the worst ratio between arterial oxygen partial pressure over oxygen inspired fraction was lower (81 (70-109) vs. 100 (80-124) mmHg, respectively, p = 0.02) and prone positioning and extracorporeal membrane oxygenation (ECMO) were more frequently used than in patients without COVID-19. COVID-19 patients had lower maximal lactate level and maximal norepinephrine dose than patients without COVID-19. Day-60 mortality was similar between groups (57% vs. 65%, respectively, p = 0.45). The maximal value of EVLWi and PVPI remained independently associated with outcome in the whole cohort. CONCLUSION: Compared to ARDS patients without COVID-19, patients with COVID-19 had similar lung mechanics, but higher EVLWi and PVPI values from the beginning of the disease. This was associated with worse oxygenation and with more requirement of prone positioning and ECMO. This is compatible with the specific lung inflammation and severe diffuse alveolar damage related to COVID-19. By contrast, patients with COVID-19 had fewer hemodynamic derangement. Eventually, mortality was similar between groups. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: ClinicalTrials.gov (NCT04337983). Registered 30 March 2020-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04337983 .


Assuntos
COVID-19/metabolismo , Permeabilidade Capilar , Água Extravascular Pulmonar/metabolismo , Síndrome do Desconforto Respiratório/metabolismo , Índice de Gravidade de Doença , COVID-19/complicações , Hemodinâmica , Humanos , Pulmão/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Prognóstico , Edema Pulmonar/metabolismo , Termodiluição
7.
Sci Rep ; 11(1): 11524, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34075155

RESUMO

Nearly 5% of patients suffering from COVID-19 develop acute respiratory distress syndrome (ARDS). Extravascular lung water index (EVLWI) is a marker of pulmonary oedema which is associated with mortality in ARDS. In this study, we evaluate whether EVLWI is higher in patients with COVID-19 associated ARDS as compared to COVID-19 negative, ventilated patients with ARDS and whether EVLWI has the potential to monitor disease progression. EVLWI and cardiac function were monitored by transpulmonary thermodilution in 25 patients with COVID-19 ARDS subsequent to intubation and compared to a control group of 49 non-COVID-19 ARDS patients. At intubation, EVLWI was noticeably elevated and significantly higher in COVID-19 patients than in the control group (17 (11-38) vs. 11 (6-26) mL/kg; p < 0.001). High pulmonary vascular permeability index values (2.9 (1.0-5.2) versus 1.9 (1.0-5.2); p = 0.003) suggested a non-cardiogenic pulmonary oedema. By contrast, the cardiac parameters SVI, GEF and GEDVI were comparable in both cohorts. High EVLWI values were associated with viral persistence, prolonged intensive care treatment and in-hospital mortality (23.2 ± 6.7% vs. 30.3 ± 6.0%, p = 0.025). Also, EVLWI showed a significant between-subjects (r = - 0.60; p = 0.001) and within-subjects correlation (r = - 0.27; p = 0.028) to Horowitz index. Compared to non COVID-19 ARDS, COVID-19 results in markedly elevated EVLWI-values in patients with ARDS. High EVLWI reflects a non-cardiogenic pulmonary oedema in COVID-19 ARDS and could serve as parameter to monitor ARDS progression on ICU.


Assuntos
COVID-19/complicações , Água Extravascular Pulmonar/imunologia , Edema Pulmonar/mortalidade , Síndrome do Desconforto Respiratório/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/mortalidade , Permeabilidade Capilar , Progressão da Doença , Água Extravascular Pulmonar/virologia , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Pulmão/irrigação sanguínea , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Monitorização Fisiológica/estatística & dados numéricos , Prognóstico , Edema Pulmonar/diagnóstico , Edema Pulmonar/imunologia , Edema Pulmonar/virologia , Respiração Artificial , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/etiologia , Síndrome do Desconforto Respiratório/terapia , Medição de Risco/métodos , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Termodiluição/métodos , Termodiluição/estatística & dados numéricos , Adulto Jovem
9.
Medicine (Baltimore) ; 100(22): e26213, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34087898

RESUMO

ABSTRACT: Pulmonary embolism (PE) is a common medical problem. Its diagnostic criteria must be reviewed to determine the need for confirmatory testing. Computed tomography pulmonary angiography (CTPA) is the current standard of care, which provides accurate diagnosis with rapid turnaround. This study aimed to estimate the diagnostic yield of CTPA in clinically suspected PE patients in a tertiary care hospital in Saudi Arabia.Radiology records of all patients with clinically suspected PE who underwent CTPA between January 1, 2012 and September 30, 2018 were reviewed retrospectively. A radiologist with 10 years of professional experience interpreted and reported all cases. The Wells score with 2 tiers (likely and unlikely) was used to raise the clinical suspicion of PE.Positive results for PE were reported in 177 out of 534 clinically suspected cases (33%). Among the positive PE cases, 143 were acute (81%) and 34 (19%) were chronic. Bilateral, right-sided, and left-sided PE were found in 115 (65%), 37 (21%), and 25 (14%) cases, respectively. Involvement of the segmental branches, subsegmental branches, and the pulmonary trunk were noted in 152 (86%), 70 (40%), and 9 cases (5%), respectively. Saddle PE was found in (4%) of the cases. The lower lobe branches (right 55%, left 53%) and the upper lobe branches (right 47%, left 41%) were the most common sites of involvement.CTPA had a higher positive detection rate for PE among clinically suspected cases than its published diagnostic yield. Adequate clinical evaluation when selecting patients for CTPA is emphasized to minimize unjustified exposure of the patients to radiation and intravenous contrast administration. It is crucial for radiologists to provide detailed reports commenting on all relevant findings, including pertinent negatives. A template for reporting radiological findings for CTPA can be recommended for this purpose.


Assuntos
Angiografia por Tomografia Computadorizada/métodos , Meios de Contraste/efeitos adversos , Pulmão/irrigação sanguínea , Embolia Pulmonar/diagnóstico , Exposição à Radiação/efeitos adversos , Administração Intravenosa , Adulto , Idoso , Angiografia por Tomografia Computadorizada/normas , Meios de Contraste/administração & dosagem , Feminino , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Artéria Pulmonar/diagnóstico por imagem , Embolia Pulmonar/epidemiologia , Exposição à Radiação/prevenção & controle , Estudos Retrospectivos , Arábia Saudita/epidemiologia , Centros de Atenção Terciária
10.
PLoS One ; 16(6): e0252478, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34101734

RESUMO

BACKGROUND: Gas exchange in COVID-19 pneumonia is impaired and vessel obstruction has been suspected to cause ventilation-perfusion mismatch. Dual-energy CT (DECT) can depict pulmonary perfusion by regional assessment of iodine uptake. OBJECTIVE: The purpose of this study was the analysis of pulmonary perfusion using dual-energy CT in a cohort of 27 consecutive patients with severe COVID-19 pneumonia. METHOD: We retrospectively analyzed pulmonary perfusion with DECT in 27 consecutive patients (mean age 57 years, range 21-73; 19 men and 8 women) with severe COVID-19 pneumonia. Iodine uptake (IU) in regions-of-interest placed into normally aerated lung, ground-glass opacifications (GGO) and consolidations was measured using a dedicated postprocessing software. Vessel enlargement (VE) within opacifications and presence of pulmonary embolism (PE) was assessed by subjective analysis. Linear mixed models were used for statistical analyses. RESULTS: Compared to normally aerated lung 106/151 (70.2%) opacifications without upstream PE demonstrated an increased IU, 9/151 (6.0%) an equal IU and 36/151 (23.8%) a decreased IU. The estimated mean iodine uptake (EMIU) in opacifications without upstream PE (GGO 1.77 mg/mL; 95%-CI: 1.52-2.02; p = 0.011, consolidations 1.82 mg/mL; 95%-CI: 1.56-2.08, p = 0.006) was significantly higher compared to normal lung (1.22 mg/mL; 95%-CI: 0.95-1.49). In case of upstream PE, EMIU of opacifications (combined GGO and consolidations) was significantly decreased compared to normal lung (0.52 mg/mL; 95%-CI: -0.07-1.12; p = 0.043). The presence of VE in opacifications correlated significantly with iodine uptake (p<0.001). CONCLUSIONS: DECT revealed the opacifications in a subset of patients with severe COVID-19 pneumonia to be perfused non-uniformly with some being hypo- and others being hyperperfused. Mean iodine uptake in opacifications (both ground-glass and consolidation) was higher compared to normally aerated lung except for areas with upstream pulmonary embolism. Vessel enlargement correlated with iodine uptake: In summary, in a cohort of 27 consecutive patients with severe COVID-19 pneumonia, dual-energy CT demonstrated a wide range of iodine uptake in pulmonary ground-glass opacifications and consolidations as a surrogate marker for hypo- and hyperperfusion compared to normally aerated lung. Applying DECT to determine which pathophysiology is predominant might help to tailor therapy to the individual patient´s needs.


Assuntos
COVID-19/diagnóstico por imagem , Pulmão , Embolia Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Meios de Contraste/química , Feminino , Humanos , Pulmão/irrigação sanguínea , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
11.
PLoS Comput Biol ; 17(5): e1008861, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33956786

RESUMO

The relationship between regional variabilities in airflow (ventilation) and blood flow (perfusion) is a critical determinant of gas exchange efficiency in the lungs. Hypoxic pulmonary vasoconstriction is understood to be the primary active regulator of ventilation-perfusion matching, where upstream arterioles constrict to direct blood flow away from areas that have low oxygen supply. However, it is not understood how the integrated action of hypoxic pulmonary vasoconstriction affects oxygen transport at the system level. In this study we develop, and make functional predictions with a multi-scale multi-physics model of ventilation-perfusion matching governed by the mechanism of hypoxic pulmonary vasoconstriction. Our model consists of (a) morphometrically realistic 2D pulmonary vascular networks to the level of large arterioles and venules; (b) a tileable lumped-parameter model of vascular fluid and wall mechanics that accounts for the influence of alveolar pressure; (c) oxygen transport accounting for oxygen bound to hemoglobin and dissolved in plasma; and (d) a novel empirical model of hypoxic pulmonary vasoconstriction. Our model simulations predict that under the artificial test condition of a uniform ventilation distribution (1) hypoxic pulmonary vasoconstriction matches perfusion to ventilation; (2) hypoxic pulmonary vasoconstriction homogenizes regional alveolar-capillary oxygen flux; and (3) hypoxic pulmonary vasoconstriction increases whole-lobe oxygen uptake by improving ventilation-perfusion matching.


Assuntos
Hipóxia/fisiopatologia , Modelos Biológicos , Circulação Pulmonar/fisiologia , Relação Ventilação-Perfusão/fisiologia , Algoritmos , Animais , Arteríolas/fisiopatologia , Fenômenos Biofísicos , Biologia Computacional , Simulação por Computador , Humanos , Pulmão/irrigação sanguínea , Pulmão/fisiopatologia , Oxigênio/fisiologia , Troca Gasosa Pulmonar/fisiologia , Ratos , Vasoconstrição/fisiologia , Vênulas/fisiopatologia
12.
Ultrasound Med Biol ; 47(8): 2331-2338, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33972153

RESUMO

Induction of pulmonary capillary hemorrhage (PCH) by lung ultrasound (LUS) depends not only on physical exposure parameters but also on physiologic conditions and drug treatment. We studied the influence of xylazine and clonidine on LUS-induced PCH in spontaneously hypertensive and normotensive rats using diagnostic B-mode ultrasound at 7.3 MHz. Using ketamine anesthesia, rats receiving saline, xylazine, or clonidine treatment were tested with different pulse peak rarefactional pressure amplitudes in 5 min exposures. Results with xylazine or clonidine in spontaneously hypertensive rats were not significantly different at the three exposure pulse peak rarefactional pressure amplitudes, and thresholds were lower (2.2 MPa) than with saline (2.6 MPa). Variations in LUS PCH were not correlated with mean systemic blood pressure. Similar to previous findings for dexmedetomidine, the clinical drug clonidine tended to increase susceptibility to LUS PCH.


Assuntos
Anti-Hipertensivos/uso terapêutico , Capilares , Clonidina/uso terapêutico , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Pulmão/irrigação sanguínea , Xilazina/uso terapêutico , Animais , Hemorragia/diagnóstico por imagem , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Ondas Ultrassônicas , Ultrassonografia
13.
Int J Biol Macromol ; 183: 695-706, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33932419

RESUMO

Implantation of biomaterials and hybrid constructs in tissue engineering approaches presents major limitations such as inflammatory reaction and the lack of vasculature integration. Therefore, new strategies are needed to enhance implant function, immune protection, and revascularization. In this work, we developed fibrous meshes composed of fucoidan (Fu), a sulfated polysaccharide extracted from brown algae, and polycaprolactone (PCL), a synthetic biodegradable polymer, using the airbrush technique. The chemical characterization by FTIR, EDS, and XPS confirmed the presence of the two polymers in the structure of airbrushed nanofibrous meshes (ANFM). Moreover, these nanofibrous exhibited good wettability and mechanical properties envisaging their application as templates for biomaterials and cell culture. The developed ANFM were directly cultured with human pulmonary microvascular endothelial (HPMEC-ST1.6R) cells for up to 7 days. Biological results demonstrated that ANFM comprising Fu promoted cellular attachment, spreading, and proliferation of human endothelial cells. The angiogenic potential of ANFM was further evaluated by onplantation of PCL and PCL/Fu ANFM in chick chorioallantoic membrane (CAM). In ovo and ex ovo results showed that the incorporation of Fu increased the pro-angiogenic potential of ANFM. Altogether, the results suggest that airbrush biocomposite meshes could be used as a biomaterial substrate to promote vascularization.


Assuntos
Indutores da Angiogênese/farmacologia , Membrana Corioalantoide/irrigação sanguínea , Pulmão/irrigação sanguínea , Poliésteres/química , Polissacarídeos/farmacologia , Indutores da Angiogênese/química , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Embrião de Galinha , Membrana Corioalantoide/efeitos dos fármacos , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Humanos , Pulmão/citologia , Pulmão/efeitos dos fármacos , Microvasos/citologia , Microvasos/efeitos dos fármacos , Nanofibras , Polissacarídeos/química , Telas Cirúrgicas , Engenharia Tecidual
14.
Carbohydr Res ; 505: 108326, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34015720

RESUMO

The viral infection caused by SARS-CoV-2 has increased the mortality rate and engaged several adverse effects on the affected individuals. Currently available antiviral drugs have found to be unsuccessful in the treatment of COVID-19 patients. The demand for efficient antiviral drugs has created a huge burden on physicians and health workers. Plasma therapy seems to be less accomplishable due to insufficient donors to donate plasma and low recovery rate from viral infection. Repurposing of antivirals has been evolved as a suitable strategy in the current treatment and preventive measures. The concept of drug repurposing represents new experimental approaches for effective therapeutic benefits. Besides, SARS-CoV-2 exhibits several complications such as lung damage, blood clot formation, respiratory illness and organ failures in most of the patients. Based on the accumulation of data, sulfated marine polysaccharides have exerted successful inhibition of virus entry, attachment and replication with known or unknown possible mechanisms against deadly animal and human viruses so far. Since the virus entry into the host cells is the key process, the prevention of such entry mechanism makes any antiviral strategy effective. Enveloped viruses are more sensitive to polyanions than non-enveloped viruses. Besides, the viral infection caused by RNA virus types embarks severe oxidative stress in the human body that leads to malfunction of tissues and organs. In this context, polysaccharides play a very significant role in providing shielding effect against the virus due to their polyanionic rich features and a molecular weight that hinders their reactive surface glycoproteins. Significantly the functional groups especially sulfate, sulfate pattern and addition, uronic acids, monosaccharides, glycosidic linkage and high molecular weight have greater influence in the antiviral activity. Moreover, they are very good antioxidants that can reduce the free radical generation and provokes intracellular antioxidant enzymes. Additionally, polysaccharides enable a host-virus immune response, activate phagocytosis and stimulate interferon systems. Therefore, polysaccharides can be used as candidate drugs, adjuvants in vaccines or combination with other antivirals, antioxidants and immune-activating nutritional supplements and antiviral materials in healthcare products to prevent SARS-CoV-2 infection.


Assuntos
Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Polissacarídeos/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Insuficiência Respiratória/tratamento farmacológico , Anticoagulantes/química , Anticoagulantes/isolamento & purificação , Antivirais/química , Antivirais/isolamento & purificação , Plaquetas/efeitos dos fármacos , Plaquetas/patologia , Plaquetas/virologia , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/virologia , Humanos , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Feófitas/química , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/virologia , Insuficiência Respiratória/complicações , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/virologia , Rodófitas/química , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade , Ésteres do Ácido Sulfúrico/química , Ligação Viral/efeitos dos fármacos , Internalização do Vírus/efeitos dos fármacos
15.
Jpn J Clin Oncol ; 51(6): 851-856, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-33855367

RESUMO

Previous reports on transarterial treatment for lung cancer were reviewed. The bronchial arterial infusion therapy has a long history since 1964. Better local control with less doses of anti-neoplastic agents was warranted by trying transarterial administration to lung and mediastinal tumors. It is reported that both primary and metastatic tumors are fed by bronchial or other systemic arteries. The bronchial arterial embolization for hemoptysis has been introduced for clinical practice since 1973. Hemoptysis by not only benign but also malignant diseases has been well controlled by embolization. In recent decades, the technical elements for transarterial treatments have markedly improved. They make it possible to carry out precise procedures of selective catheter insertion to the tumor relating arteries. Current concepts of transarterial treatment, technical aspects and treatment outcomes are summarized. Tentative result from chemo-embolization for advanced lung cancer using recent catheter techniques was also described. It provides favorable local control and survival merits. It is considered that a population of lung cancer patients can benefit from transarterial management using small doses of anti-neoplastic agents, with less complications and less medical costs.


Assuntos
Artérias Brônquicas/cirurgia , Embolização Terapêutica , Neoplasias Pulmonares/terapia , Artérias Brônquicas/patologia , Cateterismo Periférico/métodos , Progressão da Doença , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodos , Embolização Terapêutica/mortalidade , Hemoptise/etiologia , Hemoptise/patologia , Hemoptise/terapia , Humanos , Pulmão/irrigação sanguínea , Pulmão/patologia , Pulmão/cirurgia , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/patologia , Resultado do Tratamento
16.
Nat Rev Immunol ; 21(5): 319-329, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33824483

RESUMO

Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with severe disease show hyperactivation of the immune system, which can affect multiple organs besides the lungs. Here, we propose that SARS-CoV-2 infection induces a process known as immunothrombosis, in which activated neutrophils and monocytes interact with platelets and the coagulation cascade, leading to intravascular clot formation in small and larger vessels. Microthrombotic complications may contribute to acute respiratory distress syndrome (ARDS) and other organ dysfunctions. Therapeutic strategies aimed at reducing immunothrombosis may therefore be useful. Several antithrombotic and immunomodulating drugs have been proposed as candidates to treat patients with SARS-CoV-2 infection. The growing understanding of SARS-CoV-2 infection pathogenesis and how it contributes to critical illness and its complications may help to improve risk stratification and develop targeted therapies to reduce the acute and long-term consequences of this disease.


Assuntos
COVID-19/imunologia , COVID-19/patologia , Síndrome da Liberação de Citocina/patologia , Trombose Venosa/imunologia , Trombose Venosa/patologia , Coagulação Sanguínea/imunologia , Plaquetas/imunologia , Estado Terminal/terapia , Síndrome da Liberação de Citocina/imunologia , Endotélio Vascular/patologia , Fibrinolíticos/uso terapêutico , Humanos , Imunidade Inata/imunologia , Pulmão/irrigação sanguínea , Pulmão/patologia , Pulmão/virologia , Monócitos/imunologia , Neutrófilos/imunologia , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Trombose Venosa/prevenção & controle
17.
J Med Virol ; 93(9): 5390-5395, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33913549

RESUMO

Hypercoagulability and thrombosis caused by coronavirus disease 2019 (COVID-19) are related to the higher mortality rate. Because of limited data on the antiplatelet effect, we aimed to evaluate the impact of aspirin add-on therapy on the outcome of the patients hospitalized due to severe COVID-19. In this cohort study, patients with a confirmed diagnosis of severe COVID-19 admitted to Imam Hossein Medical Center, Tehran, Iran from March 2019 to July 2020 were included. Demographics and related clinical data during their hospitalization were recorded. The mortality rate of the patients was considered as the primary outcome and its association with aspirin use was assessed. Nine hundred and ninety-one patients were included, of that 336 patients (34%) received aspirin during their hospitalization and 655 ones (66%) did not. Comorbidities were more prevalent in the patients who were receiving aspirin. Results from the multivariate COX proportional model demonstrated a significant independent association between aspirin use and reduction in the risk of in-hospital mortality (0.746 [0.560-0.994], p = 0.046). Aspirin use in hospitalized patients with COVID-19 is associated with a significant decrease in mortality rate. Further prospective randomized controlled trials are needed to assess the efficacy and adverse effects of aspirin administration in this population.


Assuntos
Aspirina/uso terapêutico , COVID-19/tratamento farmacológico , Coagulação Intravascular Disseminada/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , SARS-CoV-2/patogenicidade , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Adulto , Idoso , Alanina/análogos & derivados , Alanina/uso terapêutico , Antivirais/uso terapêutico , Plaquetas/efeitos dos fármacos , Plaquetas/patologia , Plaquetas/virologia , COVID-19/complicações , COVID-19/mortalidade , COVID-19/virologia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/virologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/mortalidade , Diabetes Mellitus/virologia , Coagulação Intravascular Disseminada/complicações , Coagulação Intravascular Disseminada/mortalidade , Coagulação Intravascular Disseminada/virologia , Combinação de Medicamentos , Feminino , Mortalidade Hospitalar , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Hipertensão/mortalidade , Hipertensão/virologia , Irã (Geográfico) , Lopinavir/uso terapêutico , Pulmão/irrigação sanguínea , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/complicações , Embolia Pulmonar/mortalidade , Embolia Pulmonar/virologia , Respiração Artificial/mortalidade , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , Ritonavir/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Índice de Gravidade de Doença , Análise de Sobrevida , Resultado do Tratamento
18.
Aging (Albany NY) ; 13(8): 11954-11968, 2021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33886502

RESUMO

BACKGROUND: Metabonomics has been widely used to analyze the initiation, progress, and development of diseases. However, application of metabonomics to explore the mechanism of pulmonary arterial hypertension (PAH) are poorly reported. This study aimed to investigate the influence of atorvastatin (Ato) on metabolic pattern of rats with pulmonary hypertension. METHODS: PAH animal model was established using monocrotaline (MCT). The mean pulmonary artery pressure (mPAP) and right ventricular hypertrophy index (RVHI) were measured. The microstructure of pulmonary arterioles was observed by HE staining. Nuclear magnetic resonance was used to detect and analyze the serum metabolites. The levels of glycogen synthase kinase-3ß (GSK-3ß), hexokinase 2 (HK-2), sterol regulatory element-binding protein 1c (SREBP-1c), and carnitine palmitoyltransferase I (CPT-1) in the lung tissues were measured. RESULTS: Ato significantly improved lung function by decreasing mPAP, RVHI, wall thickness, and wall area. Differences in metabolic patterns were observed among normal, PAH, and Ato group. The levels of GSK-3ß and SREBP-1c were decreased, but HK-2 and CPT-1 were increased in the group PAH. Ato treatment markedly reversed the influence of MCT. CONCLUSION: Ato significantly improved the pulmonary vascular remodeling and pulmonary hypertension of PAH rats due to its inhibition on Warburg effect and fatty acid ß oxidation.


Assuntos
Atorvastatina/administração & dosagem , Hipertensão Pulmonar/tratamento farmacológico , Remodelação Vascular/efeitos dos fármacos , Animais , Pressão Arterial/efeitos dos fármacos , Modelos Animais de Doenças , Ácidos Graxos/metabolismo , Glicólise/efeitos dos fármacos , Humanos , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Pulmão/irrigação sanguínea , Pulmão/patologia , Masculino , Metabolômica , Monocrotalina/administração & dosagem , Monocrotalina/toxicidade , Oxirredução/efeitos dos fármacos , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/patologia , Ratos
19.
Biochem Biophys Res Commun ; 556: 199-206, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-33848934

RESUMO

Circulating cell-free hemoglobin (CFH) contributes to endothelial injury in several inflammatory and hemolytic conditions. We and others have shown that CFH causes increased endothelial permeability, but the precise mechanisms of CFH-mediated endothelial barrier dysfunction are not fully understood. Based on our previous study in a mouse model of sepsis demonstrating that CFH increased apoptosis in the lung, we hypothesized that CFH causes endothelial barrier dysfunction through this cell death mechanism. We first confirmed that CFH causes human lung microvascular barrier dysfunction in vitro that can be prevented by the hemoglobin scavenger, haptoglobin. While CFH caused a small but significant decrease in cell viability measured by the membrane impermeable DNA dye Draq7 in human lung microvascular endothelial cells, CFH did not increase apoptosis as measured by TUNEL staining or Western blot for cleaved caspase-3. Moreover, inhibitors of apoptosis (Z-VAD-FMK), necrosis (IM-54), necroptosis (necrostatin-1), ferroptosis (ferrostatin-1), or autophagy (3-methyladenine) did not prevent CFH-mediated endothelial barrier dysfunction. We conclude that although CFH may cause a modest decrease in cell viability over time, cell death does not contribute to CFH-mediated lung microvascular endothelial barrier dysfunction.


Assuntos
Apoptose , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Hemoglobinas/metabolismo , Pulmão/irrigação sanguínea , Microcirculação , Células Cultivadas , Haptoglobinas/metabolismo , Humanos , Fatores de Tempo
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