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1.
Nat Commun ; 12(1): 5922, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635666

RESUMO

Death from acute hemorrhage is a major problem in military conflicts, traffic accidents, and surgical procedures, et al. Achieving rapid effective hemostasis for pre-hospital care is essential to save lives in massive bleeding. An ideal hemostasis material should have those features such as safe, efficient, convenient, economical, which remains challenging and most of them cannot be achieved at the same time. In this work, we report a rapid effective nanoclay-based hemostatic membranes with nanoclay particles incorporate into polyvinylpyrrolidone (PVP) electrospun fibers. The nanoclay electrospun membrane (NEM) with 60 wt% kaolinite (KEM1.5) shows better and faster hemostatic performance in vitro and in vivo with good biocompatibility compared with most other NEMs and clay-based hemostats, benefiting from its enriched hemostatic functional sites, robust fluffy framework, and hydrophilic surface. The robust hemostatic bandages based on nanoclay electrospun membrane is an effective candidate hemostat in practical application.


Assuntos
Bandagens , Hemorragia/tratamento farmacológico , Hemostáticos/farmacologia , Caulim/farmacologia , Nanoestruturas/química , Ferida Cirúrgica/tratamento farmacológico , Animais , Argila/química , Modelos Animais de Doenças , Hemorragia/sangue , Hemorragia/patologia , Hemostasia/efeitos dos fármacos , Hemostáticos/química , Humanos , Caulim/química , Fígado/irrigação sanguínea , Fígado/efeitos dos fármacos , Fígado/lesões , Masculino , Nanoestruturas/administração & dosagem , Nanoestruturas/ultraestrutura , Povidona/química , Povidona/farmacologia , Ratos , Ratos Sprague-Dawley , Baço/irrigação sanguínea , Baço/efeitos dos fármacos , Baço/lesões , Ferida Cirúrgica/sangue , Ferida Cirúrgica/patologia
2.
Front Immunol ; 12: 735922, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671353

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major public health issue. COVID-19 is considered an airway/multi-systemic disease, and demise has been associated with an uncontrolled immune response and a cytokine storm in response to the virus. However, the lung pathology, immune response, and tissue damage associated with COVID-19 demise are poorly described and understood due to safety concerns. Using post-mortem lung tissues from uninfected and COVID-19 deadly cases as well as an unbiased combined analysis of histology, multi-viral and host markers staining, correlative microscopy, confocal, and image analysis, we identified three distinct phenotypes of COVID-19-induced lung damage. First, a COVID-19-induced hemorrhage characterized by minimal immune infiltration and large thrombus; Second, a COVID-19-induced immune infiltration with excessive immune cell infiltration but no hemorrhagic events. The third phenotype correspond to the combination of the two previous ones. We observed the loss of alveolar wall integrity, detachment of lung tissue pieces, fibroblast proliferation, and extensive fibrosis in all three phenotypes. Although lung tissues studied were from lethal COVID-19, a strong immune response was observed in all cases analyzed with significant B cell and poor T cell infiltrations, suggesting an exhausted or compromised immune cellular response in these patients. Overall, our data show that SARS-CoV-2-induced lung damage is highly heterogeneous. These individual differences need to be considered to understand the acute and long-term COVID-19 consequences.


Assuntos
COVID-19/mortalidade , COVID-19/patologia , Lesão Pulmonar/patologia , Alvéolos Pulmonares/patologia , Fibrose Pulmonar/patologia , Idoso , Idoso de 80 Anos ou mais , Autopsia , Linfócitos T CD8-Positivos/imunologia , Síndrome da Liberação de Citocina/mortalidade , Síndrome da Liberação de Citocina/patologia , Células Epiteliais/patologia , Feminino , Hemorragia/patologia , Humanos , Inflamação/patologia , Pulmão/patologia , Lesão Pulmonar/virologia , Linfopenia/patologia , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Masculino , Pessoa de Meia-Idade , Miócitos de Músculo Liso/patologia , Neutrófilos/imunologia , SARS-CoV-2 , Trombose/patologia
3.
Ann Agric Environ Med ; 28(3): 531-533, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34558281

RESUMO

Acquired haemophilia (AH) is a suddenly occurring severe blood diathesis that affects both males and females and is caused by autoantibodies which inhibit coagulation factor VIII. The report describes an unusual case of acquired haemophilia in which an epileptic seizure and haemorrhage into the ventricular system of the brain were the first manifestations of the disease. In addition, APTT was prolonged to 94.6 seconds and the factor VIII level was as low as 1.5%. The level of anti-FVIII antibody was extremely high - 272BU/ml. The patient did not undergo invasive diagnostic procedure or an operation. Recombinant factor VIIa was used to control the bleeding. In order to eradicate the inhibitor, the patient received prednisone and cyclophosphamide. Complete remission was achieved after 5.5 weeks of treatment.


Assuntos
Ventrículos Cerebrais/irrigação sanguínea , Hemofilia A/complicações , Convulsões/etiologia , Autoanticorpos/sangue , Ventrículos Cerebrais/diagnóstico por imagem , Fator VIII/metabolismo , Hemofilia A/diagnóstico por imagem , Hemofilia A/metabolismo , Hemofilia A/patologia , Hemorragia/diagnóstico por imagem , Hemorragia/etiologia , Hemorragia/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Convulsões/sangue , Convulsões/patologia
4.
J Forensic Leg Med ; 82: 102228, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34388443

RESUMO

Even if the Amussat's sign is known since the mid-19th century, few studies have been made in order to assess its real occurrence. In particular, the histopathologic examination of the Amussat's sign lacks in the medicolegal literature. The review of the literature shows indeed a significant range of variability (from 1.1 % up to 25 %) regarding the macroscopic detection of the Amussat's sign. In this study, the authors report that the identification of a vital Amussat's sign is important and may require the immunohistochemical staining for the Glycophorin A (a marker of vital reaction). The victim was a 63-year-old man, who was found suspended from the staircase with a rope. Both the carotid arteries were opened in situ by using fine scissors with blunt tips. A horizontal lesion (length 4 mm) of the intima of the left common carotid artery was documented. A sample was obtained; then, a standard post-fixative histopathologic examination and immunohistochemical staining for the Glycophorin A were carried out. The standard histopathologic examination only revealed the intimal laceration with a poor hemorrhagic infiltration. However, the immunohistochemical staining for the Glycophorin A allowed the clear identification of the hemorrhagic infiltration, which was documented both in the intimal laceration and in the periadventitial soft tissues. The immunohistochemical staining for the Glycophorin A can identify the vitality of an Amussat's sign. When an Amussat's sign is documented, the Glycophorin A may therefore help the forensic pathologist to differentiate a hanging death from a postmortem suspension of the body.


Assuntos
Artérias Carótidas/patologia , Glicoforinas/sangue , Túnica Íntima/patologia , Hemorragia/patologia , Humanos , Imuno-Histoquímica/métodos , Lacerações/sangue , Masculino , Pessoa de Meia-Idade , Mudanças Depois da Morte , Suicídio
5.
Sci Rep ; 11(1): 14173, 2021 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238966

RESUMO

Elephant endotheliotropic herpesvirus haemorrhagic disease (EEHV-HD) is widely acknowledged as the most common cause of mortality in young Asian elephants (Elephas maximus) in captivity. The objective of the current study was to perform a blinded, retrospective pathology review of European EEHV-HD fatalities, constituting the largest systematic assessment of EEHV-HD pathology to date. Findings between viral genotypes were compared with the aim to investigate if disseminated intravascular coagulation (DIC) could be substantiated as a significant complicating factor, thereby increasing the understanding of disease pathophysiology. Immunohistochemical staining confirmed endothelial cell (EC) damage and the presence of EC intranuclear inclusion bodies, demonstrating a direct viral cytopathic effect. Microthrombi were observed in 63% of cases in several organs, including lungs, which, together with widespread haemorrhage and thrombocytopenia reported in EEHV-HD case reports, supports the presence of overt DIC as a serious haemostatic complication of active EEHV infection. Death was attributed to widespread vascular damage with multi-organ dysfunction, including severe acute myocardial haemorrhage and subsequent cardiac failure. Systemic inflammation observed in the absence of bacterial infection may be caused by cytokine release syndrome. Findings reinforce the necessity to investigate cytokine responses and haemostatic status during symptomatic and asymptomatic EEHV viraemia, to potentially support the use of anti-inflammatory treatment in conjunction with anti-viral therapy and cardiovascular support.


Assuntos
Coagulação Intravascular Disseminada/veterinária , Coagulação Intravascular Disseminada/virologia , Elefantes/virologia , Hemorragia/veterinária , Hemorragia/virologia , Infecções por Herpesviridae/veterinária , Infecções por Herpesviridae/virologia , Herpesviridae/fisiologia , Animais , Coagulação Intravascular Disseminada/patologia , Edema/patologia , Hemorragia/patologia , Infecções por Herpesviridae/patologia , Corpos de Inclusão Viral/metabolismo , Inflamação/patologia , Linfonodos/patologia , Especificidade de Órgãos , Estudos Retrospectivos , Índice de Gravidade de Doença
6.
Ann Hematol ; 100(10): 2575-2584, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34324021

RESUMO

Thrombocytopenia at diagnosis and platelet drop within the first 6 months have an adverse effect on prognosis of MDS patients. We therefore were interested in the association and impact on prognosis of morphologic findings of megakaryocytes and platelets with platelet count at diagnosis, bleeding complications, and the drop of platelets during the course of disease. This retrospective analysis was based on 334 MDS patients from the Duesseldorf MDS registry that were followed up for blood counts, bleeding, transfusion dependency, and AML evolution and correlated with morphology of the megakaryocytes and platelets. Thrombocytopenia was found more frequently in higher risk MDS and was associated with hypocellularity of the megakaryocytes in the bone marrow. Signs of bleeding were present at diagnosis in 14% and occurred during the disease in 48% of all MDS patients. Death due to bleeding was ranked third behind infections and AML. A decrement of platelets during the first 6 months was associated with an inferior overall survival of 21 vs. 49 months and with a higher cumulative 2-year AML rate of 22.2% vs. 8.3% (p = 0.001). In a multivariate analysis, besides bone marrow blasts and karyotype, decreasing platelets were also associated with an inferior outcome. Signs of bleeding are present in a relevant number of MDS patients and account for significant morbidity and mortality in MDS. We could demonstrate the prognostic importance of decreasing platelets during the course of disease in all MDS patients, identifying patients at higher risk for death or AML progression.


Assuntos
Hemorragia/complicações , Síndromes Mielodisplásicas/complicações , Trombocitopenia/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Plaquetas/patologia , Feminino , Hemorragia/diagnóstico , Hemorragia/patologia , Humanos , Masculino , Megacariócitos/patologia , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/patologia , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Trombocitopenia/diagnóstico , Trombocitopenia/patologia , Adulto Jovem
7.
Cells ; 10(6)2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200229

RESUMO

Glioblastoma is among the tumor entities with an extreme thrombogenic potential and patients are at very high risk of developing a venous thromboembolism (VTE) over the course of the disease, with an incidence of up to 30% per year. Major efforts are currently being made to understand and gain novel insights into the underlying pathomechanisms of the development of VTE in patients with glioblastoma and to find appropriate biomarkers. Yet, patients with glioblastoma not only face a high thromboembolic risk but are also at risk of bleeding events. In the case of VTE, a therapeutic anticoagulation with low molecular weight heparin or, in the case of low bleeding risk, treatment with a direct oral anticoagulant, is recommended, according to recently published guidelines. With respect to an elevated bleeding risk in glioblastoma patients, therapeutic anticoagulation remains challenging in this patient group and prospective data for this vulnerable patient group are scarce, particularly with regard to direct oral anticoagulants.


Assuntos
Biomarcadores Tumorais/metabolismo , Glioblastoma , Hemorragia , Heparina de Baixo Peso Molecular/uso terapêutico , Tromboembolia Venosa , Glioblastoma/complicações , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patologia , Hemorragia/tratamento farmacológico , Hemorragia/etiologia , Hemorragia/metabolismo , Hemorragia/patologia , Humanos , Guias de Prática Clínica como Assunto , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/metabolismo , Tromboembolia Venosa/patologia
8.
Sci Rep ; 11(1): 13696, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34211011

RESUMO

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a lifesaving maneuver for the management of lethal torso hemorrhage. However, its prolonged use leads to distal organ ischemia-reperfusion injury (IRI) and systemic inflammatory response syndrome (SIRS). The objective of this study is to investigate the blood-based biomarkers of IRI and SIRS and the efficacy of direct intestinal cooling in the prevention of IRI and SIRS. A rat lethal hemorrhage model was produced by bleeding 50% of the total blood volume. A balloon catheter was inserted into the aorta for the implementation of REBOA. A novel TransRectal Intra-Colon (TRIC) device was placed in the descending colon and activated from 10 min after the bleeding to maintain the intra-colon temperature at 37 °C (TRIC37°C group) or 12 °C (TRIC12°C group) for 270 min. The upper body temperature was maintained at as close to 37 °C as possible in both groups. Blood samples were collected before hemorrhage and after REBOA. The organ injury biomarkers and inflammatory cytokines were evaluated by ELISA method. Blood based organ injury biomarkers (endotoxin, creatinine, AST, FABP1/L-FABP, cardiac troponin I, and FABP2/I-FABP) were all drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated these increased organ injury biomarkers. Plasma levels of pro-inflammatory cytokines TNF-α, IL-1b, and IL-17F were also drastically increased in TRIC37°C group after REBOA. TRIC12°C significantly downregulated the pro-inflammatory cytokines. In contrast, TRIC12°C significantly upregulated the levels of anti-inflammatory cytokines IL-4 and IL-10 after REBOA. Amazingly, the mortality rate was 100% in TRIC37°C group whereas 0% in TRIC12°C group after REBOA. Directly cooling the intestine offered exceptional protection of the abdominal organs from IRI and SIRS, switched from a harmful pro-inflammatory to a reparative anti-inflammatory response, and mitigated mortality in the rat model of REBOA management of lethal hemorrhage.


Assuntos
Oclusão com Balão/métodos , Hemorragia/terapia , Animais , Oclusão com Balão/efeitos adversos , Oclusão com Balão/instrumentação , Temperatura Baixa , Hemorragia/patologia , Inflamação/etiologia , Inflamação/patologia , Intestinos/lesões , Masculino , Ratos Sprague-Dawley , Ressuscitação/efeitos adversos , Ressuscitação/instrumentação , Ressuscitação/métodos
9.
Int J Mol Sci ; 22(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206377

RESUMO

Infiltration of red blood cells into atheromatous plaques and oxidation of hemoglobin (Hb) and lipoproteins are implicated in the pathogenesis of atherosclerosis. α1-microglobulin (A1M) is a radical-scavenging and heme-binding protein. In this work, we examined the origin and role of A1M in human atherosclerotic lesions. Using immunohistochemistry, we observed a significant A1M immunoreactivity in atheromas and hemorrhaged plaques of carotid arteries in smooth muscle cells (SMCs) and macrophages. The most prominent expression was detected in macrophages of organized hemorrhage. To reveal a possible inducer of A1M expression in ruptured lesions, we exposed aortic endothelial cells (ECs), SMCs and macrophages to heme, Oxy- and FerrylHb. Both heme and FerrylHb, but not OxyHb, upregulated A1M mRNA expression in all cell types. Importantly, only FerrylHb induced A1M protein secretion in aortic ECs, SMCs and macrophages. To assess the possible function of A1M in ruptured lesions, we analyzed Hb oxidation and heme-catalyzed lipid peroxidation in the presence of A1M. We showed that recombinant A1M markedly inhibited Hb oxidation and heme-driven oxidative modification of low-density lipoproteins as well plaque lipids derived from atheromas. These results demonstrate the presence of A1M in atherosclerotic plaques and suggest its induction by heme and FerrylHb in the resident cells.


Assuntos
alfa-Globulinas/metabolismo , Aterosclerose/etiologia , Aterosclerose/metabolismo , Heme/metabolismo , Hemoglobinas/metabolismo , Peroxidação de Lipídeos , Oxirredução , Aterosclerose/patologia , Biomarcadores , Doenças das Artérias Carótidas/etiologia , Doenças das Artérias Carótidas/metabolismo , Doenças das Artérias Carótidas/patologia , Células Cultivadas , Progressão da Doença , Suscetibilidade a Doenças , Hemorragia/metabolismo , Hemorragia/patologia , Humanos , Imuno-Histoquímica , Miócitos de Músculo Liso/metabolismo , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia
10.
Anticancer Res ; 41(7): 3667-3672, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34230165

RESUMO

BACKGROUND: In the oral and maxillofacial area, granulomatosis with polyangiitis (GPA) can lead to extended tissue destruction. CASE REPORT: This is a case report of a life-threatening local complication resulting from a large osseous defect in the cranial base with consecutive massive bleeding from the right internal carotid artery. Intraoperative examination and diagnostic imaging led to neuroradiological interventional treatment by embolization, and in neurosurgical and further reconstructive surgical treatment by the oral and maxillofacial surgeons. The purpose of this case report was to draw attention to the possibly life-threatening local complications of GPA and to discuss the importance of early intervention. CONCLUSION: As a prevention strategy, regular examinations including three-dimensional radiographic diagnostic imaging are important for the early detection of complications and the possible involvement of important structures.


Assuntos
Artéria Carótida Interna/patologia , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/patologia , Hemorragia/etiologia , Hemorragia/patologia , Hemorragia/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade
11.
Clin Immunol ; 229: 108764, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34089860

RESUMO

C57BL/6 mice with pristane-induced lupus develop macrophage-dependent diffuse alveolar hemorrhage (DAH), which is blocked by treatment with liver X receptor (LXR) agonists and is exacerbated by low IL-10 levels. Serp-1, a myxomavirus-encoded serpin that impairs macrophage activation and plasminogen activation, blocks DAH caused by MHV68 infection. We investigated whether Serp-1 also could block DAH in pristane-induced lupus. Pristane-induced DAH was prevented by treatment with recombinant Serp-1 and macrophages from Serp1-treated mice exhibited an anti-inflammatory M2-like phenotype. Therapy activated LXR, promoting M2 polarization and expression of Kruppel-like factor-4 (KLH4), which upregulates IL-10. In contrast, deficiency of tissue plasminogen activator or plasminogen activator inhibitor had little effect on DAH. We conclude that Serp-1 blocks pristane-induced lung hemorrhage by enhancing LXR-regulated M2 macrophage polarization and KLH4-regulated IL-10 production. In view of the similarities between DAH in pristane-treated mice and SLE patients, Serp-1 may represent a potential new therapy for this severe complication of SLE.


Assuntos
Lúpus Eritematoso Sistêmico/terapia , Macrófagos/efeitos dos fármacos , Serpinas/farmacologia , Proteínas Virais/farmacologia , Animais , Coagulação Sanguínea , Feminino , Hemorragia/sangue , Hemorragia/patologia , Hemorragia/prevenção & controle , Interleucina-10/biossíntese , Receptores X do Fígado/metabolismo , Pneumopatias/sangue , Pneumopatias/patologia , Pneumopatias/prevenção & controle , Lúpus Eritematoso Sistêmico/induzido quimicamente , Lúpus Eritematoso Sistêmico/imunologia , Macrófagos/classificação , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Myxoma virus/genética , Células RAW 264.7 , Serpinas/genética , Terpenos/toxicidade , Proteínas Virais/genética
13.
J Clin Exp Hematop ; 61(2): 109-113, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34092711

RESUMO

Thrombocytopenia, anasarca, fever, reticulin fibrosis/renal failure, and organomegaly comprise TAFRO syndrome, which was proposed as a distinct clinical entity from iMCD without TAFRO syndrome (iMCD-NOS) due to its aggressive clinical course, refractoriness to corticosteroids, presence of thrombocytopenia, increased level of alkaline phosphatase, and normal level of gammaglobulin. However, diagnosing TAFRO syndrome in its early stages is challenging because it is rare and its diagnostic criteria are complicated. We describe a patient with TAFRO syndrome and adrenal hemorrhage who demonstrated a rapid decline in her clinical condition and did not respond to steroid pulse therapy, resulting in a fatal outcome. In the early stage of her clinical course, she developed unilateral adrenal hemorrhage with mild thrombocytopenia and normal clotting times, suggesting adrenal hemorrhage as a unique manifestation of TAFRO syndrome. In general, patients with TAFRO syndrome exhibit a more aggressive clinical course and poorer outcome than those with iMCD-NOS. To ameliorate this poor prognosis, it is important to diagnose the disease early and immediately start powerful immunosuppressive agents such as tocilizumab. Based on this case, adrenal hemorrhage may suggest TAFRO syndrome, and facilitate the rapid diagnosis of this complicated and rare disease.


Assuntos
Glândulas Suprarrenais/patologia , Hiperplasia do Linfonodo Gigante/complicações , Hemorragia/complicações , Idoso , Medula Óssea/patologia , Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/patologia , Hiperplasia do Linfonodo Gigante/terapia , Feminino , Hemorragia/diagnóstico , Hemorragia/patologia , Hemorragia/terapia , Humanos
14.
Eur J Med Genet ; 64(9): 104262, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34161863

RESUMO

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease and usually involves the skin, musculoskeletal system, and kidneys. More than 30 genes have been to monogenic lupus, so far. Monogenic lupus is often characterized by an early-onset, similar family history, and syndromic appearance. Herein we present a pediatric patient with DNASE1L3 deficiency, suffering from both urticarial skin lesions, recurrent hemoptysis, and renal involvement, eventually diagnosed as this rare monogenic lupus. The patient suffered from recurrent urticarial rash and hemoptysis since the age of 15 months of age. He had microscopic hematuria, mild proteinuria, hypocomplementemia, and positive antinuclear antibody, anti-dsDNA, and antineutrophil cytoplasmic antibodies. Renal biopsy yielded immunocomplex glomerulonephritis. Due to early-onset, similar sibling history and consanguineous parents, we suspected monogenic lupus and performed whole-exome sequencing, which further revealed a homozygous T97Ifs*2 mutation (NM_004944.4: c.290_291delCA/p.Thr97Ilefs*2) in DNASE1L3 gene. In conclusion, DNASE1L3 deficiency should be thought when juvenile SLE occurs with early disease-onset, pulmonary hemorrhage, glomerulonephritis, and recurrent urticarial rash along with ANCA positivity.


Assuntos
Endodesoxirribonucleases/genética , Exantema/genética , Glomerulonefrite/genética , Hemorragia/genética , Síndromes de Imunodeficiência/genética , Pneumopatias/genética , Criança , Endodesoxirribonucleases/deficiência , Exantema/patologia , Glomerulonefrite/patologia , Hemorragia/patologia , Humanos , Síndromes de Imunodeficiência/patologia , Pneumopatias/patologia , Masculino
16.
Br J Haematol ; 195(3): 365-370, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34075578

RESUMO

There is concern that COVID-19 vaccination may adversely affect immune thrombocytopenia (ITP) patients. Fifty-two consecutive chronic ITP patients were prospectively followed after COVID-19 vaccination. Fifteen percent had no worsening of clinical symptoms but no post-vaccination platelet count; 73% had no new symptoms and no significant platelet count decline. However, 12% had a median platelet count drop of 96% within 2-5 days post vaccination with new bleeding symptoms; after rescue therapy with corticosteroids +/- intravenous immunoglobulin (IVIG), platelets recovered to >30 × 109 /l a median three days later. ITP exacerbation occurred independently of remission status, concurrent ITP treatment, or vaccine type. Safety of a second vaccine dose needs careful assessment.


Assuntos
Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Hemorragia/etiologia , Púrpura Trombocitopênica Idiopática/complicações , Corticosteroides/uso terapêutico , Adulto , Idoso , COVID-19/complicações , COVID-19/patologia , Feminino , Seguimentos , Hemorragia/patologia , Hemorragia/terapia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Prospectivos , Púrpura Trombocitopênica Idiopática/patologia , Púrpura Trombocitopênica Idiopática/terapia , Índice de Gravidade de Doença , Adulto Jovem
17.
Carbohydr Polym ; 265: 118043, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-33966826

RESUMO

Hemorrhage remains a significant cause of morbidity and mortality following trauma and during complex surgeries. A variety of nanomaterials, including oxidized cellulose nanofibers (OCNFs), have been studied to overcome the disadvantages of current commercial topical hemostats. However, the relationship between nano-structural characteristics and hemostatic efficacy of non-oxidized cellulose nanofibers (CNFs) has not been elucidated. Herein, we present the first report of the correlation between structure and hemostatic performance of CNFs. In vitro thromboelastometry studies on CNFs, synthesized by ball-milling, showed that there is an optimum balance point between the aspect ratio (AR) and specific surface area (SSA) of nanofibers in terms of their maximum contribution to platelet function and plasma coagulation. The optimized CNFs with high SSA (17 m2/g) and a high AR (166) shortened normal whole blood clotting time by 68 %, outperforming cellulose-based hemostats. Additionally, CNFs reduced clotting time in platelet-deficient blood (by 80 %) and heparinized blood (by 54 %).


Assuntos
Celulose/química , Hemostáticos/química , Nanofibras/química , Tromboelastografia/métodos , Celulose/farmacologia , Celulose Oxidada/química , Hemorragia/patologia , Hemorragia/terapia , Hemostáticos/farmacologia , Humanos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos
18.
Sci Rep ; 11(1): 10435, 2021 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-34001932

RESUMO

Hemorrhage and hemolysis with subsequent heme release are implicated in many pathologies. Endothelial cells (ECs) encounter large amount of free heme after hemolysis and are at risk of damage from exogenous heme. Here we show that hemorrhage aggravates endoplasmic reticulum (ER) stress in human carotid artery plaques compared to healthy controls or atheromas without hemorrhage as demonstrated by RNA sequencing and immunohistochemistry. In EC cultures, heme also induces ER stress. In contrast, if cultured ECs are pulsed with heme arginate, cells become resistant to heme-induced ER (HIER) stress that is associated with heme oxygenase-1 (HO-1) and ferritin induction. Knocking down HO-1, HO-2, biliverdin reductase, and ferritin show that HO-1 is the ultimate cytoprotectant in acute HIER stress. Carbon monoxide-releasing molecules (CORMs) but not bilirubin protects cultured ECs from HIER stress via HO-1 induction, at least in part. Knocking down HO-1 aggravates heme-induced cell death that cannot be counterbalanced with any known cell death inhibitors. We conclude that endothelium and perhaps other cell types can be protected from HIER stress by induction of HO-1, and heme-induced cell death occurs via HIER stress that is potentially involved in the pathogenesis of diverse pathologies with hemolysis and hemorrhage including atherosclerosis.


Assuntos
Estenose das Carótidas/complicações , Heme Oxigenase-1/metabolismo , Heme/metabolismo , Hemorragia/patologia , Placa Aterosclerótica/complicações , Biópsia , Estenose das Carótidas/sangue , Linhagem Celular , Estresse do Retículo Endoplasmático , Células Endoteliais/patologia , Endotélio Vascular/citologia , Endotélio Vascular/patologia , Técnicas de Silenciamento de Genes , Voluntários Saudáveis , Heme Oxigenase (Desciclizante)/genética , Heme Oxigenase (Desciclizante)/metabolismo , Heme Oxigenase-1/genética , Hemólise , Hemorragia/etiologia , Humanos , Placa Aterosclerótica/sangue
19.
Am J Physiol Regul Integr Comp Physiol ; 321(1): R12-R20, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34009032

RESUMO

Angiotensin II (ANG II) is a potent vasoconstrictor and may reduce renal blood flow (RBF), causing renal hypoxia. Hypotensive hemorrhage elevates plasma ANG II levels and is associated with increased risk of acute kidney injury. We hypothesized that ANG II antagonism prevents renal vasoconstriction and hypoxia caused by hemorrhage. Pigs were anaesthetized, surgically prepared, and randomized to intravenous losartan (1.5 mg·kg-1·h-1, n = 8) or an equal volume of intravenous Ringer acetate (vehicle-treated, n = 8). Hemorrhage was induced by continuous aspiration of blood to reach and sustain mean arterial pressure of <50 mmHg for 30 min. Plasma ANG II levels, hemodynamics and oxygenation were assessed 60 min prehemorrhage, 30-min after the start of hemorrhage, and 60 min posthemorrhage. Erythropoietin mRNA was analyzed in cortical and medullary tissue sampled at the end of the experiment. Hypotensive hemorrhage increased plasma ANG II levels and decreased RBF and oxygen delivery in both groups. Losartan-treated animals recovered in RBF and oxygen delivery, whereas vehicle-treated animals had persistently reduced RBF and oxygen delivery. In accordance, renal vascular resistance increased over time post hemorrhage in vehicle-treated animals but was unchanged in losartan-treated animals. Renal oxygen extraction rate and cortical erythropoietin mRNA levels increased in the vehicle group but not in the losartan group. In conclusion, ANG II antagonism alleviates prolonged renal vasoconstriction and renal hypoxia in a large animal model of hypotensive hemorrhage.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Hemorragia/patologia , Hipóxia/prevenção & controle , Rim/irrigação sanguínea , Losartan/farmacologia , Vasoconstrição/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Hemodinâmica , Hipotensão , Masculino , Oxigênio , Suínos
20.
Radiat Res ; 196(2): 156-174, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34019667

RESUMO

Coagulopathies are well documented after acute radiation exposure at hematopoietic doses, and radiation-induced bleeding is notably one of the two main causes of mortality in the hematopoietic acute radiation syndrome. Despite this, understanding of the mechanisms by which radiation alters hemostasis and induces bleeding is still lacking. Here, male Göttingen minipigs received hematopoietic doses of 60Co gamma irradiation (total body) and coagulopathies were characterized by assessing bleeding, blood cytopenia, fibrin deposition, changes in hemostatic properties, coagulant/anticoagulant enzyme levels, and markers of inflammation, endothelial dysfunction, and barrier integrity to understand if a relationship exists between bleeding, hemostatic defects, bone marrow aplasia, inflammation, endothelial dysfunction and loss of barrier integrity. Acute radiation exposure induced coagulopathies in the Göttingen minipig model of hematopoietic acute radiation syndrome; instances of bleeding were not dependent upon thrombocytopenia. Neutropenia, alterations in hemostatic parameters and damage to the glycocalyx occurred in all animals irrespective of occurrence of bleeding. Radiation-induced bleeding was concurrent with simultaneous thrombocytopenia, anemia, neutropenia, inflammation, increased heart rate, decreased nitric oxide bioavailability and endothelial dysfunction; bleeding was not observed with the sole occurrence of a single aforementioned parameter in the absence of the others. Alteration of barrier function or clotting proteins was not observed in all cases of bleeding. Additionally, fibrin deposition was observed in the heart and lungs of decedent animals but no evidence of DIC was noted, suggesting a unique pathophysiology of radiation-induced coagulopathies. These findings suggest radiation-induced coagulopathies are the result of simultaneous damage to several key organs and biological functions, including the immune system, the inflammatory response, the bone marrow and the cardiovasculature.


Assuntos
Síndrome Aguda da Radiação/patologia , Hematopoese/genética , Hemorragia/patologia , Inflamação/patologia , Anormalidades Induzidas por Radiação , Síndrome Aguda da Radiação/sangue , Síndrome Aguda da Radiação/etiologia , Animais , Transtornos de Proteínas de Coagulação/sangue , Transtornos de Proteínas de Coagulação/etiologia , Transtornos de Proteínas de Coagulação/patologia , Modelos Animais de Doenças , Hematopoese/efeitos da radiação , Hemorragia/sangue , Hemorragia/etiologia , Humanos , Inflamação/sangue , Inflamação/etiologia , Suínos , Porco Miniatura
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