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1.
Medicine (Baltimore) ; 99(39): e22341, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991448

RESUMO

RATIONALE: The Goodpasture syndrome is an extremely rare disease, with renal and pulmonary manifestations, and is mediated by anti-glomerular basement membrane (anti-GBM) antibodies. Renal pathological changes are mainly characterized by glomerular crescent formation and linear immunofluorescent staining for immunoglobulin G on the GBM. There are few reports on the atypical course of the syndrome involving serum-negative anti-GBM antibodies. Therefore, we present a case of Goodpasture syndrome that presented with nephrotic-range proteinuria and was seronegative for anti-GBM antibodies. PATIENT CONCERNS: A 38-year-old Chinese man presented with a lung lesion that was discovered by physical examination a month prior to presentation. The chief concern was occasional hemoptysis without fever, cough, chest pain, and edema. DIAGNOSES: Laboratory testing revealed that the urinary protein level and urine erythrocyte count were 7.4 g/24 hours and 144/high-power field (HPF), respectively. Serological testing for anti-GBM antibodies was negative. Chest computed tomography revealed multiple exudative lesions in both lungs, indicating alveolar infiltration and hemorrhage. Electronic bronchoscopy and pathological examination of the alveolar lavage fluid indicated no abnormalities. However, kidney biopsy suggested cellular crescent formation and segmental necrosis of the globuli, with linear IgG and complement C3 deposition on the GBM. These findings were consistent with the diagnosis of anti-GBM antibody nephritis. INTERVENTIONS: The patient underwent 7 sessions of double filtration plasmapheresis. He was also administered with intravenous methylprednisolone and cyclophosphamide. After renal function stabilization, he was discharged under an immunosuppressive regimen comprising of glucocorticoids and cyclophosphamides. OUTCOMES: Three months later, follow-up examination revealed that the 24-hour urine protein had increased to 13 g. Furthermore, the urine erythrocyte count was 243/HPF. After a 6-month follow-up, the patient achieved partial remission, with a proteinuria level of 3.9 g/24 hours and a urine erythrocyte count of 187/HPF. LESSONS: This extremely rare case of Goodpasture syndrome manifested with seronegativity for anti-GBM antibodies and nephrotic-range proteinuria. Our findings emphasize the importance of renal biopsy for the clinical diagnosis of atypical cases. Furthermore, because renal involvement achieved only partial remission despite therapy, early detection and active treatment of the Goodpasture syndrome is necessary to improve the prognosis of patients.


Assuntos
Doença Antimembrana Basal Glomerular/complicações , Doença Antimembrana Basal Glomerular/imunologia , Autoanticorpos/sangue , Proteinúria/etiologia , Administração Intravenosa , Adulto , Assistência ao Convalescente , Doença Antimembrana Basal Glomerular/diagnóstico , Doença Antimembrana Basal Glomerular/terapia , Grupo com Ancestrais do Continente Asiático/etnologia , Complemento C3/metabolismo , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Quimioterapia Combinada , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Hemoptise/diagnóstico , Hemorragia/etiologia , Hemorragia/patologia , Humanos , Imunoglobulina G/metabolismo , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Rim/patologia , Glomérulos Renais/metabolismo , Glomérulos Renais/patologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Nefrite/diagnóstico , Nefrite/imunologia , Plasmaferese/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
2.
Blood ; 136(11): 1342-1346, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32766883

RESUMO

Coronavirus disease 2019 (COVID-19) is associated with a prothrombotic state with a high incidence of thrombotic events during hospitalization; however, data examining rates of thrombosis after discharge are limited. We conducted a retrospective observational cohort study of discharged patients with confirmed COVID-19 not receiving anticoagulation. The cohort included 163 patients with median time from discharge to last recorded follow-up of 30 days (interquartile range [IQR], 17-46 days). The median duration of index hospitalization was 6 days (IQR, 3-12 days) and 26% required intensive care. The cumulative incidence of thrombosis (including arterial and venous events) at day 30 following discharge was 2.5% (95% confidence interval [CI], 0.8-7.6); the cumulative incidence of venous thromboembolism alone at day 30 postdischarge was 0.6% (95% CI, 0.1-4.6). The 30-day cumulative incidence of major hemorrhage was 0.7% (95% CI, 0.1-5.1) and of clinically relevant nonmajor bleeds was 2.9% (95% CI, 1.0-9.1). We conclude that the rates of thrombosis and hemorrhage appear to be similar following hospital discharge for COVID-19, emphasizing the need for randomized data to inform recommendations for universal postdischarge thromboprophylaxis.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Hemorragia/etiologia , Alta do Paciente/estatística & dados numéricos , Pneumonia Viral/complicações , Trombose/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Coronavirus/virologia , Feminino , Seguimentos , Hemorragia/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/virologia , Prognóstico , Estudos Retrospectivos , Trombose/patologia , Adulto Jovem
3.
J Clin Endocrinol Metab ; 105(12)2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32738040

RESUMO

CONTEXT: Bilateral adrenal hemorrhage is a rare condition with potentially life-threatening consequences such as acute adrenal insufficiency. Early adrenal axis testing, as well as directed imaging, is crucial for immediate diagnosis and treatment. Coronavirus disease 2019 (COVID-19) has been associated with coagulopathy and thromboembolic events. CASE DESCRIPTION: A 66-year-old woman presented with acute COVID-19 infection and primary adrenal insufficiency due to bilateral adrenal hemorrhage (BAH). She also had a renal vein thrombosis. Her past medical history revealed primary antiphospholipid syndrome (APLS). Four weeks after discharge she had no signs of COVID-19 infection and her polymerase chain reaction test for COVID-19 was negative, but she still needed glucocorticoid and mineralocorticoid replacement therapy. The combination of APLS and COVID-19 was probably responsible of the adrenal event as a "two-hit" mechanism. CONCLUSIONS: COVID-19 infection is associated with coagulopathy and thromboembolic events, including BAH. Adrenal insufficiency is life threatening; therefore, we suggest that early adrenal axis testing for COVID-19 patients with clinical suspicion of adrenal insufficiency should be carried out.


Assuntos
Doenças das Glândulas Suprarrenais/etiologia , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Hemorragia/etiologia , Pneumonia Viral/complicações , Trombose/etiologia , Doenças das Glândulas Suprarrenais/patologia , Idoso , Infecções por Coronavirus/virologia , Feminino , Hemorragia/patologia , Humanos , Pandemias , Pneumonia Viral/virologia , Prognóstico , Trombose/patologia
4.
Leg Med (Tokyo) ; 47: 101748, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32682296

RESUMO

The identification of muscle hemorrhage in a cadaver that is in an advanced stage of decomposition is an important but challenging task. Our study investigated whether Fourier transform infrared (FT-IR) microspectroscopy in conjunction with chemometrics could identify muscle hemorrhage using rat cadavers with advanced decomposition. In this study, an intramuscular blood injection method, instead of a mechanical injury method, was used to construct a muscle hemorrhage model, and the modeling idea of muscle hemorrhage identification was to discriminate and classify hemoglobin-leaking myofibrils from negative myofibrils. First, the optical images of hematoxylin/eosin (H&E) stained hemorrhagic muscle at different postmortem intervals (PMIs) were observed and showed that the morphological features of whole erythrocytes disappeared since the PMI of 4 d. Subsequently, principle component analysis (PCA) was performed and indicated that the biochemical differences in protein structures between fresh erythrocytes and myofibrils can be detected by the IR spectroscopic method. Ultimately, several classification models based on the partial least square discriminant analysis (PLS-DA) algorithm were successfully constructed for different PMIs and PMI ranges and achieved great prediction performances in external validations. This preliminary study demonstrates the feasibility of using FT-IR microspectroscopy combined with chemometrics as a potential approach for identifying muscle hemorrhage in cadavers with advanced decomposition for offering vital evidences in judicial process.


Assuntos
Autopsia/métodos , Patologia Legal/métodos , Hemorragia/patologia , Músculos/patologia , Doenças Musculares/patologia , Mudanças Depois da Morte , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Animais , Modelos Animais de Doenças , Eritrócitos/patologia , Masculino , Miofibrilas/patologia , Análise de Componente Principal , Ratos Sprague-Dawley
5.
J Vis Exp ; (160)2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32597878

RESUMO

Cerebral contusion is a severe medical problem affecting millions of people worldwide each year. There is an urgent need to understand the pathophysiological mechanism and to develop effective therapeutic strategy for this devastating neurological disorder. Intraparenchymal hemorrhage and post-traumatic inflammatory response induced by initial physical impact can aggravate microglia/macrophage activation and neuroinflammation which subsequently worsen brain pathology. We provide here a controlled cortical impact (CCI) protocol that can reproduce experimental cortical contusion in mice by using a pneumatic impactor system to deliver mechanical force with controllable magnitude and velocity onto the dural surface. This preclinical model allows researchers to induce moderately severe focal cerebral contusion in mice and to investigate a wide range of post-traumatic pathological progressions including hemorrhage contusion, microglia/macrophage activation, iron toxicity, axonal injury, as well as short-term and long-term neurobehavioral deficits. The present protocol can be useful for exploring the long-term effects of and potential interventions for cerebral contusion.


Assuntos
Lesões Encefálicas Traumáticas/complicações , Córtex Cerebral/patologia , Contusões/complicações , Contusões/patologia , Hemorragia/complicações , Hemorragia/patologia , Inflamação/patologia , Animais , Lesões Encefálicas Traumáticas/patologia , Craniotomia , Modelos Animais de Doenças , Inflamação/complicações , Masculino , Camundongos Endogâmicos C57BL , Bainha de Mielina/metabolismo , Técnicas Estereotáxicas
6.
Hematol Oncol ; 38(4): 589-596, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32588912

RESUMO

The anticoagulant treatment for patients with hematologic malignancies is low molecular weight heparin (LMWH), which is considered the safest in this particular patients setting. Although direct oral anticoagulants (DOACs) have proven their efficacy and safety in patients with cancer, their use can be challenging in patients with hematologic malignancies due to the peculiarity of these neoplasms: high thrombotic risk, possible onset of thrombocytopenia and concomitant anticancer therapies. The aim of our study was to evaluate the efficacy and safety of DOACs for venous thromboembolism or atrial fibrillation in patients with hematologic malignancies and plasmatic DOACs level during anticancer therapy and at time of bleeding or thrombotic complications. We evaluated patients with hematologic malignancies treated with DOACs for venous thromboembolism or atrial fibrillation-therapy was maintained until the platelet count was ≥50 × 109 /L. In case of concomitant anticancer treatment and haemorrhagic or thrombotic events, we checked DOACs plasma levels (trough and peak). The patients evaluated were 135: 104/135 were on anticancer therapy. We did not observe either thrombotic or major haemorrhagic adverse events. Minor bleedings occurred in 10 patients and clinical relevant non-major (CRNM) in two patients. There was a statistically significant correlation between bleedings and myelodysplastic syndrome. DOACs resulted effective and safe in patients with hematologic malignancies. DOACs plasma level can be helpful in suggesting an early dose adjustment to prevent haemorrhagic adverse event in patients on concomitant anticancer therapy. Larger prospective studies including hematologic patients are warranted to confirm the safety and efficacy of DOACs.


Assuntos
Anticoagulantes/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Fibrilação Atrial/tratamento farmacológico , Neoplasias Hematológicas/tratamento farmacológico , Hemorragia/tratamento farmacológico , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/induzido quimicamente , Fibrilação Atrial/patologia , Feminino , Seguimentos , Neoplasias Hematológicas/patologia , Hemorragia/induzido quimicamente , Hemorragia/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Tromboembolia Venosa/induzido quimicamente , Tromboembolia Venosa/patologia
7.
Leuk Res ; 94: 106356, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32445941

RESUMO

Hemorrhagic death is the leading cause of treatment failure in acute promyelocytic leukemia (APL). Our ability to identify patients at greatest risk of hemorrhage, and to actively prevent hemorrhage, remains limited. Nevertheless, some data is available to guide contemporary clinical practice and future investigation. Circulating disease burden, best represented by the peripheral WBC / blast count, is the most consistent predictor of major and fatal bleeding risk. In contrast, laboratory markers of disseminated intravascular coagulation (DIC) appear to be poor predictors. A number of interventions have been posited to reduce bleeding risk. Prompt initiation of all-trans retinoic acid (ATRA), avoidance of invasive procedures, transfusion support, and cytoreduction all have theoretical merit. Though they lack strong evidence to support their benefit with respect to bleeding, they are associated with limited risks, and are therefore advisable. Low-dose therapeutic heparin and antifibrinolytics have not shown the ability to positively modify bleeding risk, and heparin has been associated with harm. Thrombomodulin has shown promise in limited retrospective studies however further prospective data are needed. rFVIIa may have a role in cases of life-threatening bleeding however evidence is largely anecdotal. Additional studies evaluating the above interventions, and investigating other potential interventions are needed.


Assuntos
Crise Blástica , Hemorragia , Leucemia Promielocítica Aguda , Crise Blástica/sangue , Crise Blástica/complicações , Crise Blástica/tratamento farmacológico , Crise Blástica/patologia , Fator VIII/uso terapêutico , Hemorragia/sangue , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Hemorragia/patologia , Heparina/uso terapêutico , Humanos , Leucemia Promielocítica Aguda/sangue , Leucemia Promielocítica Aguda/complicações , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/patologia , Trombomodulina/uso terapêutico , Tretinoína/uso terapêutico
8.
PLoS One ; 15(4): e0231739, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32352989

RESUMO

OBJECTIVES: We previously reported microvascular leakage resulting from fibrinogen-γ chain C-terminal products (γC) occurred via a RhoA-dependent mechanism. The objective of this study was to further elucidate the signaling mechanism by which γC induces endothelial hyperpermeability. Since it is known that γC binds and activates endothelial αvß3, a transmembrane integrin receptor involved in intracellular signaling mediated by the tyrosine kinases FAK and Src, we hypothesized that γC alters endothelial barrier function by activating the FAK-Src pathway leading to junction dissociation and RhoA driven cytoskeletal stress-fiber formation. METHODS AND RESULTS: Using intravital microscopy of rat mesenteric microvessels, we show increased extravasation of plasma protein (albumin) resulting from γC administration. In addition, capillary fluid filtration coefficient (Kfc) indicated γC-induced elevated lung vascular permeability. Furthermore, γC decreased transendothelial barrier resistance in a time-dependent and dose-related fashion in cultured rat lung microvascular endothelial cells (RLMVECs), accompanied by increased FAK/Src phosphorylation detection by western blot. Experiments with pharmacological inhibition or gene silencing of FAK showed significantly reduced γC-induced albumin and fluid leakage across microvessels, stress-fiber formation, VE-cadherin tyrosine phosphorylation, and improved γC-induced endothelial barrier dysfunction, indicating the involvement of FAK in γC mediated hyperpermeability. Comparable results were found when Src was targeted in a similar manner, however inhibition of FAK prevented Src activation, suggesting that FAK is upstream of Src in γC-mediated hyperpermeability. In addition, γC-induced cytoskeletal stress-fiber formation was attenuated during inhibition or silencing of these tyrosine kinases, concomitantly with RhoA inhibition. CONCLUSION: The FAK-Src pathway contributes to γC-induced microvascular barrier dysfunction, junction protein phosphorylation and disorganization in a manner that involves RhoA and stress-fiber formation.


Assuntos
Permeabilidade Capilar/fisiologia , Quinase 1 de Adesão Focal/metabolismo , Hemorragia/patologia , Microvasos/patologia , Quinases da Família src/metabolismo , Animais , Permeabilidade Capilar/efeitos dos fármacos , Linhagem Celular , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/patologia , Fibrinogênio/toxicidade , Quinase 1 de Adesão Focal/antagonistas & inibidores , Quinase 1 de Adesão Focal/genética , Hemorragia/induzido quimicamente , Humanos , Microscopia Intravital , Pulmão/irrigação sanguínea , Masculino , Mesentério/irrigação sanguínea , Mesentério/diagnóstico por imagem , Microvasos/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Fosforilação/genética , RNA Interferente Pequeno/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Proteínas rho de Ligação ao GTP/metabolismo , Quinases da Família src/genética
9.
AJNR Am J Neuroradiol ; 41(5): 836-843, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32273265

RESUMO

BACKGROUND AND PURPOSE: Identifying the mere presence of carotid intraplaque hemorrhage would be insufficient to accurately discriminate the presence of acute cerebral infarct. We aimed to investigate the association between signal intensity ratios of carotid intraplaque hemorrhage on T1-weighted MR imaging and acute cerebral infarct in patients with hemorrhagic carotid plaques using MR vessel wall imaging. MATERIALS AND METHODS: Symptomatic patients with carotid intraplaque hemorrhage were included. The signal intensity ratios of carotid intraplaque hemorrhage against muscle on T1-weighted, TOF, and MPRAGE images were measured. The acute cerebral infarct was determined on the hemisphere ipsilateral to the carotid intraplaque hemorrhage. The association between signal intensity ratios of carotid intraplaque hemorrhage and acute cerebral infarct was analyzed. RESULTS: Of 109 included patients (mean, 66.8 ± 9.9 years of age; 96 men), 40 (36.7%) had acute cerebral infarct. Patients with acute cerebral infarct had significantly higher signal intensity ratios of carotid intraplaque hemorrhage on T1-weighted images than those without (Median, 1.44; 25-75 Percentiles, 1.14-1.82 versus Median, 1.27; 25-75 Percentiles, 1.06-1.55, P = .022). Logistic regression analysis revealed that the signal intensity ratio of carotid intraplaque hemorrhage on T1-weighted images was significantly associated with acute cerebral infarct before (OR, 4.08; 95% CI, 1.34-12.40; P = .013) and after (OR, 3.34; 95% CI, 1.08-10.31; P = .036) adjustment for clinical confounding factors. However, this association was not significant when further adjusted for occlusion of the carotid artery (P = .058) and volumes of intraplaque hemorrhage and lipid-rich necrotic core (P = .458). CONCLUSIONS: The signal intensity ratio of carotid intraplaque hemorrhage on T1-weighted images is associated with acute cerebral infarct in symptomatic patients with carotid hemorrhagic plaques. This association is independent of traditional risk factors but not of the size of plaque composition. The possibility of applying T1 signals of carotid intraplaque hemorrhage to predict subsequent cerebrovascular ischemic events needs to be prospectively verified.


Assuntos
Estenose das Carótidas/diagnóstico por imagem , Infarto Cerebral/etiologia , Hemorragia/diagnóstico por imagem , Neuroimagem/métodos , Placa Aterosclerótica/diagnóstico por imagem , Idoso , Estenose das Carótidas/complicações , Estenose das Carótidas/patologia , Estudos Transversais , Feminino , Hemorragia/complicações , Hemorragia/patologia , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Imagem por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/complicações , Placa Aterosclerótica/patologia , Fatores de Risco
10.
Basic Res Cardiol ; 115(3): 24, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32140789

RESUMO

Intramyocardial hemorrhage is an independent predictor of adverse outcomes in ST-segment elevation myocardial infarction (STEMI). Iron deposition resulting from ischemia-reperfusion injury (I/R) is pro-inflammatory and has been associated with adverse remodeling. The role of iron chelation in hemorrhagic acute myocardial infarction (AMI) has never been explored. The purpose of this study was to investigate the cardioprotection offered by the iron-chelating agent deferiprone (DFP) in a porcine AMI model by evaluating hemorrhage neutralization and subsequent cardiac remodeling. Two groups of animals underwent a reperfused AMI procedure: control and DFP treated (N = 7 each). A comprehensive MRI examination was performed in healthy state and up to week 4 post-AMI, followed by histological assessment. Infarct size was not significantly different between the two groups; however, the DFP group demonstrated earlier resolution of hemorrhage (by T2* imaging) and edema (by T2 imaging). Additionally, ventricular enlargement and myocardial hypertrophy (wall thickness and mass) were significantly smaller with DFP, suggesting reduced adverse remodeling, compared to control. The histologic results were consistent with the MRI findings. To date, there is no effective targeted therapy for reperfusion hemorrhage. Our proof-of-concept study is the first to identify hemorrhage-derived iron as a therapeutic target in I/R and exploit the cardioprotective properties of an iron-chelating drug candidate in the setting of AMI. Iron chelation could potentially serve as an adjunctive therapy in hemorrhagic AMI.


Assuntos
Cardiotônicos/farmacologia , Deferiprona/uso terapêutico , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Quelantes de Ferro/uso terapêutico , Infarto do Miocárdio/complicações , Miocárdio/patologia , Remodelação Ventricular/efeitos dos fármacos , Animais , Cardiotônicos/farmacocinética , Cardiotônicos/uso terapêutico , Deferiprona/farmacocinética , Deferiprona/farmacologia , Modelos Animais de Doenças , Feminino , Hemorragia/patologia , Quelantes de Ferro/farmacocinética , Quelantes de Ferro/farmacologia , Infarto do Miocárdio/patologia , Suínos
12.
Clin Dermatol ; 38(1): 3-18, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32197746

RESUMO

Hemorrhagic rashes are observed in a wide variety of conditions, ranging from harmless to life-threatening. This review offers a stepwise approach, which helps limit the possible differential diagnoses based on the clinical manifestations and the clinical picture. The most common and most important conditions, including infectious, coagulation and embolic disorders, vasculitides, and vasculopathies, are briefly reviewed focusing on morphology. Dermatologists often need to distinguish among infectious, reactive, or autoimmune etiologies of the rash and determine if the condition is dangerous or even life-threatening in order to make the right decision. Dermatologic expertise provides vital input in the diagnosis and care of complex interdisciplinary patients, such as those with sepsis, purpura fulminans, and thrombotic thrombocytopenic purpura.


Assuntos
Exantema/patologia , Pele/patologia , Diagnóstico Diferencial , Exantema/complicações , Exantema/diagnóstico , Hemorragia/etiologia , Hemorragia/patologia , Humanos
13.
Oxid Med Cell Longev ; 2020: 3721383, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32184915

RESUMO

Intraplaque hemorrhage frequently occurs in atherosclerotic plaques resulting in cell-free hemoglobin, which is oxidized to ferryl hemoglobin (FHb) in the highly oxidative environment. Osteoclast-like cells (OLCs) derived from macrophages signify a counterbalance mechanism for calcium deposition in atherosclerosis. Our aim was to investigate whether oxidized hemoglobin alters osteoclast formation, thereby affecting calcium removal from mineralized atherosclerotic lesions. RANKL- (receptor activator of nuclear factor kappa-Β ligand-) induced osteoclastogenic differentiation and osteoclast activity of RAW264.7 cells were studied in response to oxidized hemoglobin via assessing bone resorption activity, expression of osteoclast-specific genes, and the activation of signalization pathways. OLCs in diseased human carotid arteries were assessed by immunohistochemistry. FHb, but not ferrohemoglobin, decreased bone resorption activity and inhibited osteoclast-specific gene expression (tartrate-resistant acid phosphatase, calcitonin receptor, and dendritic cell-specific transmembrane protein) induced by RANKL. In addition, FHb inhibited osteoclastogenic signaling pathways downstream of RANK (receptor activator of nuclear factor kappa-Β). It prevented the induction of TRAF6 (tumor necrosis factor (TNF) receptor-associated factor 6) and c-Fos, phosphorylation of p-38 and JNK (c-Jun N-terminal kinase), and nuclear translocation of NFκB (nuclear factor kappa-Β) and NFATc1 (nuclear factor of activated T-cells, cytoplasmic 1). These effects were independent of heme oxygenase-1 demonstrated by knocking down HO-1 gene in RAW264.7 cells and in mice. Importantly, FHb competed with RANK for RANKL binding suggesting possible mechanisms by which FHb impairs osteoclastic differentiation. In diseased human carotid arteries, OLCs were abundantly present in calcified plaques and colocalized with regions of calcium deposition, while the number of these cells were lower in hemorrhagic lesions exhibiting accumulation of FHb despite calcium deposition. We conclude that FHb inhibits RANKL-induced osteoclastic differentiation of macrophages and suggest that accumulation of FHb in a calcified area of atherosclerotic lesion with hemorrhage retards the formation of OLCs potentially impairing calcium resorption.


Assuntos
Diferenciação Celular , Hemoglobinas/farmacologia , Hemorragia/patologia , Macrófagos/patologia , Osteoclastos/patologia , Placa Aterosclerótica/patologia , Animais , Reabsorção Óssea/patologia , Calcinose , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/patologia , Diferenciação Celular/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Biológicos , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Osteogênese/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Placa Aterosclerótica/genética , Ligação Proteica/efeitos dos fármacos , Ligante RANK/genética , Ligante RANK/metabolismo , Células RAW 264.7 , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
Postgrad Med ; 132(3): 288-295, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32027205

RESUMO

OBJECTIVES: This study aimed to assess various types of safety lancets in terms of blood volume and pain perception during capillary blood sampling, a routine finger-puncture procedure for obtaining a small amount of human blood for running various screening and diagnostic tests. METHODS: Data were collected from 100 adult healthy volunteers following finger-puncture procedure. Four different types of safety lancets were tested (Acti-Lance, Prolance, Medlance Plus, and MediSafe Solo). Each type has its own versions, giving 16 different safety lancets in total. RESULTS: A significant difference in the mean capillary blood volume was found between blade and needle equipped safety lancets. MediSafe Solo type lancet had no blade version, and hence its use was associated with the lowest mean collected capillary blood volume (42.4 µL). Acti-Lance and Medlance Plus type lancets had one blade version and the mean collected capillary blood volume was 82.2 and 99.0 µL, respectively. Prolance type lancet had two blade versions, and its use was associated with the highest mean capillary blood volume (118.3 µL). The level of pain intensity was evaluated as low by the majority of patients for all lancets. Medlance Plus was the least painful and Acti-Lance was the most painful type of safety lancet. On a 0-to-10 scale of pain, 75% of punctures were assessed by the participants at a level not exceeding 3 points. CONCLUSIONS: This study suggests that although all investigated safety lancets achieve adequate performance regarding the necessary capillary blood volume to run a diagnostic of test, lancets equipped with blades differ significantly from those equipped with needles in terms of the mean obtained capillary blood volume. Further, although all devices produced relatively low levels of pain, the amount of pain caused by blade versions of safety lancets has been found to be higher than that of needle versions. CLINICALTRIALS.GOV ID: NCT04001348. (https://clinicaltrials.gov/ct2/show/NCT04001348?term=NCT04001348&draw=2&rank=1).


Assuntos
Coleta de Amostras Sanguíneas/efeitos adversos , Coleta de Amostras Sanguíneas/instrumentação , Hemorragia/patologia , Percepção da Dor , Adolescente , Adulto , Idoso , Dedos , Humanos , Pessoa de Meia-Idade , Agulhas , Estudos Prospectivos , Método Simples-Cego , Adulto Jovem
15.
Intern Med ; 59(10): 1303-1308, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32023586

RESUMO

Acquired factor X deficiency (AFXD) is a very rare coagulation disorder. A 40-year-old man with no comorbidities suffering from a fever, malaise, and severe hemorrhagic symptoms, including massive hematuria, was emergently admitted. His platelet count was normal, but his prothrombin time and activated partial thromboplastin time were markedly prolonged, which was thought to be due to autoantibody against a coagulation factor in the common pathway. Despite severe massive hematuria resulting in transient renal failure, he was successfully treated with urgent immunosuppressive therapy. Computed tomography revealed bronchopneumonia, which improved with antibiotic administration. AFXD without evidence of amyloidosis was subsequently diagnosed.


Assuntos
Deficiência do Fator X/complicações , Hemorragia/etiologia , Hemorragia/patologia , Infecções Respiratórias/complicações , Adulto , Testes de Coagulação Sanguínea , Deficiência do Fator X/diagnóstico , Hematúria/complicações , Humanos , Masculino , Tempo de Tromboplastina Parcial , Tempo de Protrombina
16.
Sci Rep ; 10(1): 3008, 2020 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-32080300

RESUMO

Several proteins and peptides in saliva were shown to stimulate gingival wound repair, but the role of salivary metabolites in this process remains unexplored. In vitro gingival re-epithelialization kinetics were determined using unstimulated saliva samples from healthy individuals collected during an experimental gingivitis study. Elastic net regression with stability selection identified a specific metabolite signature in a training dataset that was associated with the observed re-epithelialization kinetics and enabled its prediction for all saliva samples obtained in the clinical study. This signature encompassed ten metabolites, including plasmalogens, diacylglycerol and amino acid derivatives, which reflect enhanced host-microbe interactions. This association is in agreement with the positive correlation of the metabolite signature with the individual's gingival bleeding index. Remarkably, intra-individual signature-variation over time was associated with elevated risk for gingivitis development. Unravelling how these metabolites stimulate wound repair could provide novel avenues towards therapeutic approaches in patients with impaired wound healing capacity.


Assuntos
Eritritol/uso terapêutico , Gengiva/efeitos dos fármacos , Gengivite/metabolismo , Hemorragia/metabolismo , Metaboloma , Saliva/metabolismo , Adolescente , Adulto , Aminoácidos/metabolismo , Aminoácidos/farmacologia , Bioensaio , Estudos de Casos e Controles , Linhagem Celular , Diglicerídeos/metabolismo , Diglicerídeos/farmacologia , Suscetibilidade a Doenças , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Feminino , Gengiva/metabolismo , Gengiva/microbiologia , Gengiva/patologia , Gengivite/tratamento farmacológico , Gengivite/microbiologia , Gengivite/patologia , Hemorragia/tratamento farmacológico , Hemorragia/microbiologia , Hemorragia/patologia , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Plasmalogênios/metabolismo , Plasmalogênios/farmacologia , Reepitelização/efeitos dos fármacos , Reepitelização/fisiologia , Saliva/química , Saliva/microbiologia , Índice de Gravidade de Doença , Streptococcus mutans/crescimento & desenvolvimento , Streptococcus mutans/patogenicidade
17.
Sci Rep ; 10(1): 2825, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32071350

RESUMO

Blood transfusion is fundamental in managing hematologic malignancies. We sought to evaluate the need and availability of blood products for patients with hematological malignancies at Uganda Cancer Institute. We prospectively studied the demand and supply of blood for patients with thrombocytopenia (platelet count ≤50 × 109/L), anemia (hemoglobin ≤10 g/dL), and bleeding (WHO grade ≥2). We used Poisson generalized estimating equation regression models for longitudinal binary outcomes. Among 91 patients, the median age was 26 years (IQR, 11-47). Thrombocytopenia occurred on ≥1 day in 58% of patients and on 49% of hospital days. Platelets were transfused to 39% of patients. The mean number of platelet units requested per day was 16.2 (range 0-30); 5.1 (range 0-15) were received. Anemia occurred on ≥1 day in 90% of patients; on 78% of days; and 68% received at least one blood transfusion. The mean number of blood units requested was 36.3 (range 8-57) units per day; 14 (range 0-30) were received. Bleeding occurred on ≥1 day in 19% of patients on 8% of hospital days. Thrombocytopenia and anemia were common, but product availability was substantially below that requested. We recommend increased blood collection and adherence to strict transfusion triggers as strategies to improve blood availability.


Assuntos
Plaquetas , Transfusão de Sangue , Neoplasias Hematológicas/epidemiologia , Transfusão de Plaquetas , Adolescente , Adulto , África ao Sul do Saara/epidemiologia , Anemia/sangue , Anemia/epidemiologia , Anemia/patologia , Criança , Feminino , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/patologia , Hemoglobinas/metabolismo , Hemorragia/sangue , Hemorragia/epidemiologia , Hemorragia/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Trombocitopenia/sangue , Trombocitopenia/epidemiologia , Trombocitopenia/patologia , Adulto Jovem
18.
Am J Forensic Med Pathol ; 41(1): 1-4, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31977349

RESUMO

The popularity of e-cigarettes (vaping) has been on the rise in recent years, but the adverse effects of vaping have been greatly unknown. In 2019, the use of vaping products has been linked to an outbreak of severe lung disease, some cases of which have progressed to death. One death attributed to vaping is presented with emphasis on the gross and histopathological findings from the autopsy. These findings were correlated with the patient's clinical course and medicolegal investigation to determine the cause of death. To our knowledge, this is the first confirmed death in the United States that was directly attributed to the use of vaping.


Assuntos
Lesão Pulmonar Aguda/patologia , Sistemas Eletrônicos de Liberação de Nicotina , Pulmão/patologia , Síndrome do Desconforto Respiratório do Adulto/patologia , Vaping/efeitos adversos , Lesão Pulmonar Aguda/etiologia , Adulto , Canabinoides , Proliferação de Células , Pneumonia em Organização Criptogênica/diagnóstico , Feminino , Fibroblastos/patologia , Patologia Legal , Hemorragia/patologia , Humanos , Hipertensão , Hipertrofia Ventricular Esquerda/patologia , Macrófagos/patologia , Miocárdio/patologia , Obesidade Mórbida , Tamanho do Órgão , Óleos Vegetais , Alvéolos Pulmonares/patologia , Síndrome do Desconforto Respiratório do Adulto/etiologia , Estados Unidos , Remodelação Vascular
19.
Nat Commun ; 11(1): 356, 2020 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-31953383

RESUMO

Glycosylation is critical to megakaryocyte (MK) and thrombopoiesis in the context of gene mutations that affect sialylation and galactosylation. Here, we identify the conserved B4galt1 gene as a critical regulator of thrombopoiesis in MKs. ß4GalT1 deficiency increases the number of fully differentiated MKs. However, the resulting lack of glycosylation enhances ß1 integrin signaling leading to dysplastic MKs with severely impaired demarcation system formation and thrombopoiesis. Platelets lacking ß4GalT1 adhere avidly to ß1 integrin ligands laminin, fibronectin, and collagen, while other platelet functions are normal. Impaired thrombopoiesis leads to increased plasma thrombopoietin (TPO) levels and perturbed hematopoietic stem cells (HSCs). Remarkably, ß1 integrin deletion, specifically in MKs, restores thrombopoiesis. TPO and CXCL12 regulate ß4GalT1 in the MK lineage. Thus, our findings establish a non-redundant role for ß4GalT1 in the regulation of ß1 integrin function and signaling during thrombopoiesis. Defective thrombopoiesis and lack of ß4GalT1 further affect HSC homeostasis.


Assuntos
Galactosiltransferases/metabolismo , Células-Tronco Hematopoéticas/metabolismo , Homeostase , Integrina beta1/metabolismo , Trombopoese/fisiologia , Animais , Plaquetas/metabolismo , Plaquetas/patologia , Adesão Celular , Diferenciação Celular , Quimiocina CXCL12/metabolismo , Colágeno , Modelos Animais de Doenças , Fibronectinas , Galactosiltransferases/genética , Predisposição Genética para Doença , Hemorragia/genética , Hemorragia/metabolismo , Hemorragia/patologia , Integrina beta1/genética , Laminina , Ligantes , Megacariócitos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Transdução de Sinais , Trombocitopenia/genética , Trombocitopenia/metabolismo , Trombocitopenia/patologia , Trombopoese/genética , Trombopoetina/sangue
20.
Vet Surg ; 49(3): 472-479, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31916608

RESUMO

OBJECTIVE: To determine the prognostic value of (1) colonic venous lactate or peripheral lactate values obtained before and after manual correction of a large colon volvulus and (2) a combination of variables including pelvic flexure biopsy. STUDY DESIGN: Prospective clinical study. ANIMALS: Forty adult horses in which large colon volvulus was diagnosed intraoperatively. METHODS: Colonic venous, peripheral venous, and arterial blood samples were collected to measure lactate values before and after manual correction. Mucosal biopsy samples were obtained in cases that underwent enterotomy or colonic resection and anastomosis. Interstitium to crypt (I:C) ratio and hemorrhage scores were measured. Optimal cutoff values were determined by receiver operator curve analysis, and associations between variables and short-term outcome were determined by univariable regression. Short-term survival was defined as horses being discharged from the hospital. P ≤ .05 was considered significant. RESULTS: No association was found between colonic venous lactate values before (P = .011) or after (P = .201) manual correction of large colon volvulus and determination of short-term outcome. Peripheral venous lactate at admission ≥3.2 mmol/L and after manual correction ≥5 mmol/L, arterial lactate postmanual correction ≥3.53 mmol/L, and histomorphometric measurements of mucosal hemorrhage ≥3 and I:C ratio > 1 were associated with poor short-term outcome. CONCLUSION: Peripheral lactate values, histomorphometric measures of I:C ratio, and hemorrhage score provided prognostic information that could help guide recommendations made to owners. CLINICAL SIGNIFICANCE: Peripheral lactate values after manual correction provide important intraoperative diagnostic information to assist in predicting case outcome in the operative and immediately postoperative period.


Assuntos
Colo/patologia , Doenças dos Cavalos/sangue , Doenças dos Cavalos/diagnóstico , Volvo Intestinal/veterinária , Lactatos/sangue , Animais , Biópsia/veterinária , Gasometria/veterinária , Feminino , Hemorragia/patologia , Doenças dos Cavalos/terapia , Cavalos , Volvo Intestinal/sangue , Volvo Intestinal/diagnóstico , Volvo Intestinal/terapia , Masculino , Prognóstico , Estudos Prospectivos
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