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1.
Crit Care ; 24(1): 605, 2020 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046113

RESUMO

BACKGROUND: Systemic inflammation in COVID-19 often leads to multiple organ failure, including acute kidney injury (AKI). Renal replacement therapy (RRT) in combination with sequential extracorporeal blood purification therapies (EBP) might support renal function, attenuate systemic inflammation, and prevent or mitigate multiple organ dysfunctions in COVID-19. AIM: Describe overtime variations of clinical and biochemical features of critically ill patients with COVID-19 treated with EBP with a hemodiafilter characterized by enhanced cytokine adsorption properties. METHODS: An observational prospective study assessing the outcome of patients with COVID-19 admitted to the ICU (February to April 2020) treated with EBP according to local practice. Main endpoints included overtime variation of IL-6 and multiorgan function-scores, mortality, and occurrence of technical complications or adverse events. RESULTS: The study evaluated 37 patients. Median baseline IL-6 was 1230 pg/ml (IQR 895) and decreased overtime (p < 0.001 Kruskal-Wallis test) during the first 72 h of the treatment, with the most significant decrease in the first 24 h (p = 0.001). The reduction in serum IL-6 concentrations correlated with the improvement in organ function, as measured in the decrease of SOFA score (rho = 0.48, p = 0.0003). Median baseline SOFA was 13 (IQR 6) and decreased significantly overtime (p < 0.001 at Kruskal-Wallis test) during the first 72 h of the treatment, with the most significant decrease in the first 48 h (median 8 IQR 5, p = 0.001). Compared to the expected mortality rates, as calculated by APACHE IV, the mean observed rates were 8.3% lower after treatment. The best improvement in mortality rate was observed in patients receiving EBP early on during the ICU stay. Premature clotting (running < 24 h) occurred in patients (18.9% of total) which featured higher effluent dose (median 33.6 ml/kg/h, IQR 9) and higher filtration fraction (median 31%, IQR 7.4). No electrolyte disorders, catheter displacement, circuit disconnection, unexpected bleeding, air, or thromboembolisms due to venous cannulation of EBP were recorded during the treatment. In one case, infection of vascular access occurred during RRT, requiring replacement. CONCLUSIONS: EBP with heparin-coated hemodiafilter featuring cytokine adsorption properties administered to patients with COVID-19 showed to be feasible and with no adverse events. During the treatment, patients experienced serum IL-6 level reduction, attenuation of systemic inflammation, multiorgan dysfunction improvement, and reduction in expected ICU mortality rate.


Assuntos
Infecções por Coronavirus/terapia , Citocinas/sangue , Hemodiafiltração/instrumentação , Hemodiafiltração/métodos , Pneumonia Viral/terapia , Infecções por Coronavirus/sangue , Humanos , Unidades de Terapia Intensiva , Pandemias , Projetos Piloto , Pneumonia Viral/sangue , Estudos Prospectivos , Resultado do Tratamento
2.
Medicine (Baltimore) ; 99(41): e22607, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031316

RESUMO

Ikaros family zinc finger 1(IKZF1) encodes a lymphoid-restricted zinc finger transcription factor named Ikaros that regulates lymphocyte differentiation and proliferation as well as self-tolerance. Increasing evidence indicates that IKZF1 could contribute to the pathogenesis of autoimmune diseases. Recent research has provided evidence that IKZF1 might correlate with Systemic lupus erythematosus (SLE), but no clear definition has been made yet. In this study, we focus on the relationship between IKZF1 polymorphisms and SLE susceptibility, cytokine levels, and clinical characteristics in the Chinese Han population.One thousand seventy-six subjects, including 400 SLE patients and 676 healthy controls, were included in this study. Three single nucleotide polymorphisms within IKZF1 containing rs4917014, rs11980379, and rs4132601 were genotyped in all subjects by an improved multiplex ligation detection reaction technique. 143 subjects from SLE patients were randomly selected for testing the levels of serum cytokines. The clinical characteristics of SLE patients were gathered and collated from medical records. The data were analyzed mainly using SPSS20.0 (SPSS lnc., Chicago, IL).Significant relationships were observed between rs4132601 and SLE susceptibility, CD40 ligand, and malar rash (P < .001, P = .04, and P = .01, respectively). In addition, significant relationships were observed between rs4917014 and susceptibility, granzyme B level, and hematological disorder in SLE (P = .005, P = .03 and P = .005, respectively).The results further support that IKZF1 may have an important role in the development and pathogenesis of SLE. Allele G of rs4132601 and rs4917014 is related to a decreased risk of SLE occurrence and associated with clinical features in SLE patients, including CD40 ligand level, granzyme B level, malar rash, and hematological disorder, which play important roles in disease progression.


Assuntos
Citocinas/sangue , Fator de Transcrição Ikaros/genética , Lúpus Eritematoso Sistêmico/genética , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Desequilíbrio de Ligação , Lúpus Eritematoso Sistêmico/sangue , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Adulto Jovem
3.
Front Immunol ; 11: 565521, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013930

RESUMO

Neurological disorders caused by neuroviral infections are an obvious pathogenic manifestation. However, non-neurotropic viruses or peripheral viral infections pose a considerable challenge as their neuropathological manifestations do not emerge because of primary infection. Their secondary or bystander pathologies develop much later, like a syndrome, during and after the recovery of patients from the primary disease. Massive inflammation caused by peripheral viral infections can trigger multiple neurological anomalies. These neurological damages may range from a general cognitive and motor dysfunction up to a wide spectrum of CNS anomalies, such as Acute Necrotizing Hemorrhagic Encephalopathy, Guillain-Barré syndrome, Encephalitis, Meningitis, anxiety, and other audio-visual disabilities. Peripheral viruses like Measles virus, Enteroviruses, Influenza viruses (HIN1 series), SARS-CoV-1, MERS-CoV, and, recently, SARS-CoV-2 are reported to cause various neurological manifestations in patients and are proven to be neuropathogenic even in cellular and animal model systems. This review presents a comprehensive picture of CNS susceptibilities toward these peripheral viral infections and explains some common underlying themes of their neuropathology in the human brain.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Inflamação Neurogênica/complicações , Inflamação Neurogênica/imunologia , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Vírus da SARS/imunologia , Síndrome Respiratória Aguda Grave/complicações , Animais , Barreira Hematoencefálica/imunologia , Barreira Hematoencefálica/virologia , Infecções por Coronavirus/virologia , Citocinas/sangue , Modelos Animais de Doenças , Humanos , Microglia/imunologia , Microglia/virologia , Inflamação Neurogênica/virologia , Pandemias , Pneumonia Viral/virologia , Síndrome Respiratória Aguda Grave/imunologia , Síndrome Respiratória Aguda Grave/virologia
4.
Acta Med Indones ; 52(3): 306-313, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33020343

RESUMO

Cytokine storm in COVID-19 infection is an excessive immune response to external stimuli where the pathogenesis is complex. The disease progresses rapidly and the mortality is high. Certain evidence shows that the severe deterioration of some patients has been closely related to the strong upregulation of cytokine production in SARS-Co-V2 induced pneumonia with an associated cytokine storm syndrome. Identification of existing approaved therapy with proven safety profile to treat hyperinflammation is critical unmet need in order to reduce COVID-19 associated mortality. To date, no specific therapeutic drugs are available to treat COVID-19 infection. Preliminary studies have shown that immune-modulatory or immune suppressive treatments might be considered as treatment choices for COVID-19, particularly in severe disease. This article review the pathogenesis and treatment strategies of COVID-19 virus-induced inflammatory storm in attempt to provide valuable medication guidance for clinical treatment.


Assuntos
Betacoronavirus , Infecções por Coronavirus/imunologia , Citocinas/sangue , Gerenciamento Clínico , Imunidade Inata , Pandemias , Pneumonia Viral/imunologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Citocinas/imunologia , Humanos , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia
5.
Mediators Inflamm ; 2020: 6914878, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061829

RESUMO

Background: COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has threatened every civilian as a global pandemic. The immune system poses the critical interactive chain between the human body and the virus. Here, we make efforts to examine whether comorbidity with type 2 diabetes (T2D) affects the immunological response in COVID-19 patients. Methods: We conducted a retrospective pilot study investigating immunological characteristics of confirmed cases of COVID-19 with or without comorbid T2D. Two subcohorts of sex- and age-matched participants were eligible for data analysis, of which 33 participants were with T2D and the remaining 37 were nondiabetic (NDM). Cellular immunity was assessed by flow cytometric determination of surface markers including CD3, CD4, CD8, CD19, CD16, and CD56 in peripheral blood. Levels of C reactive protein, immunoglobulin (IgG, IgM, IgA, and IgE), and complements (C3, C4) were detected by rate nephelometry immunoassay. And Th1/Th2 cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ) were detected by Cytometric Bead Array. Results: Neutrophil counts were found to be significantly higher in the T2D group than in the NDM group and had a significant relevance with clinical severity. Lymphocyte frequencies showed no significant differences in the two groups. However, the proportions and absolute counts of T, Tc, Th, and NK cells decreased in both groups to different degrees. An abnormal increase in neutrophil count and a decrease in lymphocyte subpopulations may represent risk factors of COVID-19 severity. The level of IgG, IgM, IgA, C3, and C4 showed no significant difference between the two groups, while the IgE levels were higher in the T2D group than in the NDM group (p < 0.05). Th1 cytokines including IFN-γ, TNF-α, and IL-6, as well as CRP, appeared significantly higher in the T2D group. Conclusions: The COVID-19 patients comorbid with T2D demonstrated distinguishable immunological parameters, which represented clinical relevancies with the predisposed disease severity in T2D.


Assuntos
Betacoronavirus , Infecções por Coronavirus/imunologia , Diabetes Mellitus Tipo 2/imunologia , Pneumonia Viral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos de Coortes , Comorbidade , Proteínas do Sistema Complemento/metabolismo , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Citocinas/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Imunidade Celular , Imunoglobulinas/sangue , Mediadores da Inflamação/sangue , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Projetos Piloto , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Estudos Retrospectivos , Células Th1/imunologia , Células Th2/imunologia
6.
Open Biol ; 10(9): 200160, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32961074

RESUMO

Coronavirus disease 2019 (COVID-19) has swept the world, unlike any other pandemic in the last 50 years. Our understanding of the disease has evolved rapidly since the outbreak; disease prognosis is influenced mainly by multi-organ involvement. Acute respiratory distress syndrome, heart failure, renal failure, liver damage, shock and multi-organ failure are strongly associated with morbidity and mortality. The COVID-19 disease pathology is plausibly linked to the hyperinflammatory response of the body characterized by pathological cytokine levels. The term 'cytokine storm syndrome' is perhaps one of the critical hallmarks of COVID-19 disease severity. In this review, we highlight prominent cytokine families and their potential role in COVID-19, the type I and II interferons, tumour necrosis factor and members of the Interleukin family. We address various changes in cellular components of the immune response corroborating with changes in cytokine levels while discussing cytokine sources and biological functions. Finally, we discuss in brief potential therapies attempting to modulate the cytokine storm.


Assuntos
Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/patologia , Citocinas/sangue , Pneumonia Viral/patologia , Betacoronavirus/imunologia , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/tratamento farmacológico , Humanos , Inflamação/patologia , Pandemias
7.
PLoS One ; 15(9): e0239532, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32976531

RESUMO

To investigate the clinical value of changes in the subtypes of peripheral blood lymphocytes and levels of inflammatory cytokines in patients with COVID-19, the total numbers of lymphocytes and CD4+ lymphocytes and the ratio of CD4+/CD8+ lymphocytes were calculated and observed in different groups of patients with COVID-19. The results show that the lymphocytopenia in patients with COVID-19 was mainly manifested by decreases in the CD4+ T lymphocyte number and the CD4+/CD8+ ratio. The decreased number of CD4+ T lymphocytes and the elevated levels of TNF-α and IL-6 were correlated with the severity of COVID-19 disease.


Assuntos
Linfócitos T CD4-Positivos/patologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/imunologia , Citocinas/sangue , Pneumonia Viral/sangue , Pneumonia Viral/imunologia , Adolescente , Adulto , Idoso , Betacoronavirus , Contagem de Linfócito CD4 , Relação CD4-CD8 , Criança , Infecções por Coronavirus/diagnóstico , Feminino , Humanos , Interleucina-6/sangue , Linfopenia/sangue , Linfopenia/patologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangue
8.
J Environ Pathol Toxicol Oncol ; 39(3): 247-260, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32865916

RESUMO

The anticancer activity of malvidin was studied in Dalton's lymphoma ascites (DLA)-induced solid and ascitic tumor mice models. Malvidin is a natural compound belonging to the family of O-methylated anthocyanidin and plays a predominant role in regulating both short- and long-term cellular activities. Animals were injected with DLA cells (1.5 × 106 cells/animal) to induce solid and ascitic tumors. The administration of malvidin (5 mg/kg bw and 10 mg/kg bw) was carried out for 10 consecutive days from the day of tumor induction for both solid and ascitic tumors. Cyclophosphamide, CTX (25 mg/kg bw), used as the standard drug, was also administered for 10 consecutive days. Treatment with malvidin showed a significant reduction in tumor volume and elevated white blood cell (WBC) count when compared to the DLA-bearing control animals. The treatment also maintained the body weight and hemoglobin level, and decreases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT) were also noted. This investigation also reported the decreased levels of cellular glutathione (GSH) in ascitic tumor groups. Malvidin reduced inflammatory mediator and cytokine levels, such as tumor necrosis factor level alpha (TNF-α) and interleukin-6 (IL-6), which serve as molecular targets for cancer prevention. A decrease in the level of reactive oxygen species (ROS), like nitric oxide (NO), was observed. Histopathological examination revealed altered morphological changes in tumor tissue and the alleviation of hepatic architecture due to DLA. Immunohistochemical analysis revealed the inhibition of iNOS. This study demonstrated that malvidin exhibited significant in vivo antitumor activity and that it was reasonably imputable to its increasing endogenous mechanism. We accent the pertinence of malvidin as a potential naturally derived drug target for tumor control.


Assuntos
Antocianinas/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Ascite/tratamento farmacológico , Citocinas/sangue , Linfoma/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Antocianinas/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Ascite/metabolismo , Ascite/patologia , Biomarcadores/sangue , Biomarcadores/metabolismo , Linhagem Celular Tumoral , Citocinas/metabolismo , Linfoma/metabolismo , Linfoma/patologia , Masculino , Camundongos , Transplante de Neoplasias , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Estresse Oxidativo/imunologia
9.
Benef Microbes ; 11(5): 477-488, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32877228

RESUMO

Neonatal calf diarrhoea is one of the challenges faced by intensive farming, and probiotics are considered a promising approach to improve calves' health. The objective of this study was to evaluate the effect of potential probiotic lactobacilli on new-born dairy calves' growth, diarrhoea incidence, faecal score, cytokine expression in blood cells, immunoglobulin A (IgA) levels in plasma and faeces, and pathogen abundance in faeces. Two in vivo assays were conducted at the same farm in two annual calving seasons. Treated calves received one daily dose of the selected lactobacilli (Lactobacillus reuteri TP1.3B or Lactobacillus johnsonii TP1.6) for 10 consecutive days. A faecal score was recorded daily, average daily gain (ADG) was calculated, and blood and faeces samples were collected. Pathogen abundance was analysed by absolute qPCR in faeces using primers directed at Salmonella enterica, rotavirus, coronavirus, Cryptosporidium parvum and three Escherichia coli virulence genes (eae, clpG and Stx1). The faecal score was positively affected by the administration of both lactobacilli strains, and diarrhoea incidence was significantly lower in treated calves. No differences were found regarding ADG, cytokine expression, IgA levels and pathogen abundance. Our findings showed that oral administration of these strains could improve gastrointestinal health, but results could vary depending on the calving season, which may be related to pathogen seasonality and other environmental effects.


Assuntos
Doenças dos Bovinos/terapia , Diarreia , Lactobacillus johnsonii/metabolismo , Lactobacillus reuteri/metabolismo , Probióticos/uso terapêutico , Animais , Animais Recém-Nascidos , Bovinos , Doenças dos Bovinos/microbiologia , Doenças dos Bovinos/prevenção & controle , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/veterinária , Criptosporidiose/prevenção & controle , Citocinas/sangue , Indústria de Laticínios , Diarreia/prevenção & controle , Diarreia/terapia , Diarreia/veterinária , Infecções por Escherichia coli/prevenção & controle , Infecções por Escherichia coli/veterinária , Fezes/virologia , Trato Gastrointestinal/microbiologia , Imunoglobulina A/sangue , Infecções por Rotavirus/prevenção & controle , Infecções por Rotavirus/veterinária , Salmonelose Animal/prevenção & controle
10.
Acta Biomed ; 91(3): e2020034, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32921728

RESUMO

Current data suggest that during the global pandemic of COVID 19 children are less affected than adults and most of them are asymptomatic or with mild symptoms. However, recently, cases of pediatric patients who have developed severe inflammatory syndrome temporally related to SARS-CoV-2 have been reported both in USA and Europe. These reports, although sharing features with other pediatric syndromes such as Kawasaki disease (KD), Kawasaki disease shock syndrome (KDSS), macrophage activated syndrome (MAS) and shock toxic syndrome (TSS), seem to outline a novel entity syndrome, characterized by cytokine storm with elevated inflammatory markers and typical clinical finding. Clinical characteristics are greater median age than KD, higher frequency of cardiac involvement and gastrointestinal symptoms, lower frequency of coronary anomalies. We report a summary of the current evidence about clinical features, pathogenesis, therapy strategies and outcome of this novel syndrome.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Citocinas/sangue , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Biomarcadores/sangue , Criança , Infecções por Coronavirus/sangue , Humanos , Síndrome de Linfonodos Mucocutâneos/sangue , Pneumonia Viral/sangue
11.
Pediatr Infect Dis J ; 39(10): e321-e324, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32932334

RESUMO

Although first considered a benign infection, recent studies have disclosed severe and potentially lethal inflammatory manifestations of COVID-19 in children. We report the case of a 4-year-old child with a post-infectious multisystem inflammatory syndrome associated with COVID-19, with a Kawasaki-like shock and prominent neurologic features, for whom a cytokine storm and reduced brain-derived neurotrophic factor were well documented.


Assuntos
Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Síndrome de Resposta Inflamatória Sistêmica/complicações , Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Fator Neurotrófico Derivado do Encéfalo/sangue , Pré-Escolar , Citocinas/sangue , Feminino , Humanos , Imunoglobulina G/sangue , Inflamação , Pandemias , Síndrome de Resposta Inflamatória Sistêmica/patologia , Síndrome de Resposta Inflamatória Sistêmica/virologia
12.
Sci Transl Med ; 12(564)2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-32958614

RESUMO

Children and youth infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have milder disease than do adults, and even among those with the recently described multisystem inflammatory syndrome, mortality is rare. The reasons for the differences in clinical manifestations are unknown but suggest that age-dependent factors may modulate the antiviral immune response. We compared cytokine, humoral, and cellular immune responses in pediatric (children and youth, age <24 years) (n = 65) and adult (n = 60) patients with coronavirus disease 2019 (COVID-19) at a metropolitan hospital system in New York City. The pediatric patients had a shorter length of stay, decreased requirement for mechanical ventilation, and lower mortality compared to adults. The serum concentrations of interleukin-17A (IL-17A) and interferon-γ (IFN-γ), but not tumor necrosis factor-α (TNF-α) or IL-6, were inversely related to age. Adults mounted a more robust T cell response to the viral spike protein compared to pediatric patients as evidenced by increased expression of CD25+ on CD4+ T cells and the frequency of IFN-γ+ CD4+ T cells. Moreover, serum neutralizing antibody titers and antibody-dependent cellular phagocytosis were higher in adults compared to pediatric patients with COVID-19. The neutralizing antibody titer correlated positively with age and negatively with IL-17A and IFN-γ serum concentrations. There were no differences in anti-spike protein antibody titers to other human coronaviruses. Together, these findings demonstrate that the poor outcome in hospitalized adults with COVID-19 compared to children may not be attributable to a failure to generate adaptive immune responses.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Hospitalização , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Adolescente , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Criança , Infecções por Coronavirus/sangue , Citocinas/sangue , Feminino , Humanos , Imunoglobulina G/metabolismo , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Glicoproteína da Espícula de Coronavírus/metabolismo , Resultado do Tratamento
13.
J Korean Med Sci ; 35(35): e324, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32893524

RESUMO

Coronavirus disease 2019 (COVID-19) is an ongoing pandemic infection associated with high morbidity and mortality. The Korean city of Daegu endured the first large COVID-19 outbreak outside of China. Since the report of the first confirmed case in Daegu on February 18, 2020, a total of 6,880 patients have been reported until May 29, 2020. We experienced five patients with ischemic stroke and COVID-19 during this period in four tertiary hospitals in Daegu. The D-dimer levels were high in all three patients in whom D-dimer blood testing was performed. Multiple embolic infarctions were observed in three patients and suspected in one. The mean time from stroke symptom onset to emergency room arrival was 22 hours. As a result, acute treatment for ischemic stroke was delayed. The present case series report raises the possibility that the coronavirus responsible for COVID-19 causes or worsens stroke, perhaps by inducing inflammation. The control of COVID-19 is very important; however, early and proper management of stroke should not be neglected during the epidemic.


Assuntos
Infecções por Coronavirus/patologia , Citocinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Pneumonia Viral/patologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Serviços Médicos de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , República da Coreia/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Tromboembolia/patologia , Terapia Trombolítica/métodos , Tempo para o Tratamento
14.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 32(4): 361-366, 2020 Aug 24.
Artigo em Chinês | MEDLINE | ID: mdl-32935509

RESUMO

OBJECTIVE: To investigate the protective effect of recombinant adult serine protease inhibitor from Trichinella spiralis (TsadSPI) on sepsis-associated acute kidney injury in mice. METHODS: A total of 18 male BALB/c mice were randomly divided into the sham-operation group, the model group, and the TsadSPI treatment group, of 6 mice in each group. Sepsis-associated acute kidney injury was modeled in the model group and TsadSPI treatment group by cecal ligation puncture (CLP), while mice in the sham-operation group were only given exploratory laparotomy without ligation or perforation of the cecum. After 30 min of CLP, mice in the sham-operation group and the model group were intraperitoneally injected with PBS (100 µL), and mice in the TsadSPI treatment group were intraperitoneally injected with PBS (100 µL) containing TsadSPI (2 µg). At 12 h following modeling, the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr) and urea nitrogen (BUN) were measured to assess the liver and kidney functions, and the changes of the mouse kidney structure were observed using HE staining. In addition, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and transforming growth factor (TGF)-ß were measured using an enzyme-linked immunosorbent assay (ELISA), and the myeloid differentiation factor 88 (MyD88) and nuclear factor kappa-B (NF-κB) p65 expression was determined in kidney tissues using immunohistochemical staining. RESULTS: At 12 h following CLP, there were significant differences in the serum levels of ALT (F = 41.031, P < 0.001), AST (F = 54.757, P < 0.001), Cr (F = 24.142, P < 0.001) and BUN (F = 214.849, P < 0.001) among the three groups, and higher levels of ALT, AST, Cr and BUN were measured in model group than in the sham-operation group (P < 0.001), while lower ALT, AST, Cr and BUN levels were found in the TsadSPI treatment group than in the model group (P < 0.001). HE staining showed severe mouse kidney injuries following CLP, and TsadSPI treatment resulted in remarkable alleviation of the injury. ELISA measured significant differences in the TNF-α (F = 47.502, P < 0.001) and IL-6 levels (F = 222.061, P < 0.001) among the three groups, and showed a remarkable reduction in the TNF-α and IL-6 levels in the TsadSPI treatment group as compared to those in the model group (P < 0.001). In addition, there were significant differences in serum IL-10 (F = 16.227, P < 0.001) and TGF-ß levels (F = 52.092, P < 0.001) among the three groups, and higher IL-10 and TGF-ß levels were seen in the TsadSPI treatment group than in the model group (P < 0.001). Immunohistochemical staining showed greater MyD88 expression and a higher nuclear positive rate of NF-κB p65 in kidney tissues in the model group than in the TsadSPI treatment group. CONCLUSIONS: TsadSPI may reduce the MyD88 expression and nuclear positive rate of NF-κB p65 in mouse kidney tissues to up-regulate the expression of immunomodulatory factors and down-regulate the expression of pro-inflammatory cytokines, thereby protecting sepsis-associated acute kidney injury.


Assuntos
Lesão Renal Aguda , Sepse , Trichinella spiralis , Lesão Renal Aguda/tratamento farmacológico , Lesão Renal Aguda/etiologia , Animais , Citocinas/sangue , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Distribuição Aleatória , Sepse/complicações , Inibidores de Serino Proteinase/genética , Inibidores de Serino Proteinase/farmacologia , Inibidores de Serino Proteinase/uso terapêutico , Trichinella spiralis/química , Trichinella spiralis/genética
15.
Circ J ; 84(10): 1679-1685, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32908073

RESUMO

The health crisis due to coronavirus disease 2019 (COVID-19) has shocked the world, with more than 1 million infections and casualties. COVID-19 can present from mild illness to multi-organ involvement, but especially acute respiratory distress syndrome. Cardiac injury and arrhythmias, including atrial fibrillation (AF), are not uncommon in COVID-19. COVID-19 is highly contagious, and therapy against the virus remains premature and largely unknown, which makes the management of AF patients during the pandemic particularly challenging. We describe a possible pathophysiological link between COVID-19 and AF, and therapeutic considerations for AF patients during this pandemic.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Antiarrítmicos/uso terapêutico , Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Fibrilação Atrial/fisiopatologia , Ablação por Cateter/métodos , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Citocinas/sangue , Interações Medicamentosas , Humanos , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Risco
16.
Yonsei Med J ; 61(9): 789-796, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32882763

RESUMO

PURPOSE: The prevalence of Mycobacterium tuberculosis (M. tb) and the status of M. bovis BCG vaccination may affect host immune responses to M. tb antigens. Understanding of the predominant local M. tb strain and immune signatures induced by its strain-specific antigens may contribute to an improved diagnosis of tuberculosis (TB). The aim of this study was to determine immune responses to M. tb antigen which was identified from the hyper-virulent Beijing/K strain in South Korea. MATERIALS AND METHODS: Pulmonary TB patients (n=52) and healthy subjects (n=92) including individuals with latent TB infection (n=31) were recruited, and QuantiFERON-TB Gold In-Tube tests were performed. The Beijing/K-antigen specific immune signatures were examined by diluted whole blood assays and multiplex bead arrays in a setting where nationwide BCG vaccination is employed. RESULTS: Statistical analyses demonstrated that three [C-X-C motif chemokine (CXCL10), interleukin (IL)-6, interferon (IFN)-α] of 17 cytokines/chemokines distinguished active cases from healthy controls following stimulation with the Beijing/K-specific antigen. IFN-α also differentiated between active diseases and latent TB infection (p<0.01), and the detection rate of TB was dramatically increased in combination with IL-6 and CXCL10 at the highest levels of specificity (95-100%). CONCLUSION: Our data indicate that immune signatures to the M. tb Beijing/K-specific antigen can provide useful information for improved TB diagnostics. The antigen may be developed as a diagnostic marker or a vaccine candidate, particularly in regions where the M. tb Beijing/K strain is endemic.


Assuntos
Tuberculose Latente/diagnóstico , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Pulmonar/diagnóstico , Adolescente , Adulto , Antígenos de Bactérias/sangue , Antígenos de Bactérias/genética , Antígenos de Superfície/sangue , Antígenos de Superfície/genética , Proteínas de Bactérias , Pequim , Estudos de Casos e Controles , Citocinas/sangue , Feminino , Humanos , Mycobacterium tuberculosis/imunologia , Mycobacterium tuberculosis/metabolismo , República da Coreia , Sensibilidade e Especificidade
17.
Front Immunol ; 11: 1844, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32903555

RESUMO

With the onset of the global pandemic in 2020 of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), there has been increasing research activity around certain disease-modifying drugs that are used for the management of inflammatory disorders such as rheumatoid arthritis, spondyloarthrosis, psoriatic arthritis, systemic lupus erythematosus, and inflammatory bowel disease for managing coronavirus symptoms. In the conditions mentioned, many people are on long-term treatment with agents including hydroxychloroquine, tumor necrosis factor alpha (TNFα) inhibitor drugs, other biologic agents such as monoclonal antibodies to IL-6 and Janus kinase inhibitors including baricitinib and tofacitinib, which are used to control inflammatory responses in their respective auto-immune condition. There is emerging data that immunomodulatory drugs could be protective at reducing certain features of SARS-CoV-2 and improving recovery. In addition, it is important to understand if subjects being treated with the immunomodulatory agents described have a less severe SARS-CoV-2 infection, as they are deemed some protection from their immunomodulatory treatment, or if they develop infections similar to non-immunocompromised patients. There is a huge unmet clinical need to advise patients responsibly about whether they should remain on their immunomodulatory treatment or not in light of Covid-19 infection. In this article we will discuss potential treatment options for SARS-CoV-2 using immunomodulatory drugs and at what stage of the condition they may be beneficial. Viable treatment options during the global coronavirus pandemic are a much-needed and an intensely active area of research.


Assuntos
Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Imunomodulação/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Colchicina/uso terapêutico , Síndrome da Liberação de Citocina/tratamento farmacológico , Citocinas/sangue , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Pessoa de Meia-Idade , Pandemias , Fatores de Risco , Fator de Necrose Tumoral alfa/antagonistas & inibidores
18.
Medicine (Baltimore) ; 99(31): e21491, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756180

RESUMO

BACKGROUND: To investigate the effect of high-volume hemofiltration (HVHF) on Th17/Treg imbalance in patients with severe acute pancreatitis (SAP). METHODS: Forty-two patients with SAP were randomly received 24 hours of continuous HVHF (n = 21) or without HVHF (n = 21). At day 28, all 42 patients were divided into survival group (n = 32) and non-survival group (n = 10). Venous blood samples collected at 0, 6, 12, and 24 hours during HVHF treatment (or equivalent time in non-HVHF group) were assessed by flow cytometry to detect Th17 and Treg cells. Concentrations of IL-6, IL-17, IL-10, and TGF-ß1 were detected by enzyme-linked immunosorbent assay. RESULTS: Th17%, Treg%, Th17/Treg, and levels of related cytokines were significantly higher in SAP patients than healthy controls (P < .05), and these changes were more pronounced in SAP patients with multiple organ failure than those with single organ failure (P < .05). After HVHF treatment, Th17%, Treg%, Th17/Treg, IL-6, IL-17, and IL-10 significantly reduced (P < .05), while there were no significant changes in non-HVHF group (P > .05). In addition, acute physiology and chronic health evaluation II and sequential organ failure assessment scores decreased markedly after HVHF treatment. Baselines of Th17%, Treg%, Th17/Treg, and related cytokines were significantly higher in non-survival group than survival group. Both acute physiology and chronic health evaluation I score and IL-6 level were positively correlated with Th17% before and after HVHF treatment (P < .01). CONCLUSIONS: Th17/Treg imbalance is present in SAP and may be correlated with its severity and prognosis. HVHF effectively attenuates the Th17/Treg imbalance in SAP patients. The beneficial effect of HVHF on Th17/Treg imbalance is possibly associated with removing excess inflammatory mediators.


Assuntos
Hemofiltração/métodos , Pancreatite/sangue , Pancreatite/terapia , Linfócitos T Reguladores/metabolismo , Células Th17/metabolismo , Doença Aguda , Adulto , Idoso , Citocinas/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/mortalidade , Insuficiência de Múltiplos Órgãos/terapia , Pancreatite/mortalidade , Resultado do Tratamento , Adulto Jovem
19.
Medicine (Baltimore) ; 99(31): e21509, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756187

RESUMO

BACKGROUND: Multiple system atrophy (MSA) is a fatal neurodegenerative disease that progresses very rapidly and has a poor prognosis. Some studies indicate that the level of inflammatory cytokines may be related to MSA. However, no consistent conclusion has been drawn yet. The purpose of our research is to perform a meta-analysis to investigate whether the level of inflammatory cytokines is altered in MSA. METHODS: Case-control studies on inflammatory cytokine levels in MSA will be searched in the following 3 databases: PubMed, Embase, and Web of Science from the database start time to March 17, 2020. Two independent authors will conduct research selection, data extraction, and quality evaluation. Data synthesis, subgroup analysis, sensitivity analysis, and the meta-analysis will be performed using Stata15.0 software. RESULTS: This study will provide a comprehensive review of all studies on inflammatory cytokine levels in MSA. CONCLUSION: To the best of our knowledge, this study will be the first meta-analysis that provides the quantitative evidence of inflammatory cytokine levels in MSA. REGISTRATION NUMBER: INPLASY202060034.


Assuntos
Citocinas/sangue , Atrofia de Múltiplos Sistemas/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Metanálise como Assunto , Atrofia de Múltiplos Sistemas/mortalidade , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
20.
Front Immunol ; 11: 1692, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32754162

RESUMO

Coronavirus-induced disease-2019 (COVID-19) continues to cause significant morbidity and mortality worldwide. While studies on SARS-CoV-2 effects on immune cell function continue to progress, we know very little about the significance of depletion of key immune effectors by the virus in the mortality and morbidity of the disease. This commentary outlines what is the reported literature thus far on the effect of virus on NK cells known to kill virally infected cells. It also underscores the necessity for the future comprehensive studies of NK cells in SARS-CoV-2 infected individuals and animal models to better understand the role and significance of reported NK cell depletion and functional inactivation in disease morbidity and mortality, in hope to design effective therapeutic interventions for the disease.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Imunoterapia/métodos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Adulto , Idoso , Animais , Linfócitos T CD8-Positivos/imunologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/virologia , Citocinas/sangue , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Subfamília C de Receptores Semelhantes a Lectina de Células NK/metabolismo , Neutrófilos/imunologia , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/virologia
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