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1.
Medicine (Baltimore) ; 100(11): e24861, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33725958

RESUMO

BACKGROUND: Sepsis is a systemic inflammatory response caused by infection, which is a common complication after severe infection, trauma, shock, and surgery, and is also an important factor in inducing septic shock and multiple organ dysfunction syndrome (MODS), and has become one of the important causes of death in critically ill patients. Septic patients with gastrointestinal transport function weakened, are prone to malnutrition, resulting in decreased immune function, thereby affecting the therapeutic effect. Clinical practice shows that the nutritional metabolism and immune response of patients with sepsis can be effectively improved by giving alanyl glutamine nutritional support treatment, but there is no evidence of evidence-based medicine. The study carried out in this protocol aims to evaluate the effectiveness of alanyl glutamine in nutritional support therapy for patients with sepsis. METHODS: The Cochrane Library, PubMed, Embase, Web of Science, WHO International Clinical Trials Registry Platform, CNKI, CBM, VIP, and Wanfang databases were searched by computer, to retrieve all randomized controlled trials (RCTs) on nutritional support for the treatment of sepsis with alanyl glutamine from the date of database establishment to December 2020. Two researchers independently selected the study, extracted and managed the data. RevMan5.3 software was used to analyze the included literature. RESULTS: This study observed the changes of serum albumin (ALB), prealbumin (PAB), hemoglobin (Hb), C-reactive protein (CRP), immunoglobulin (IgG, IgA, and IgM), APACHE II score before and after treatment to evaluate the efficacy of alanyl glutamine in nutritional support therapy for patients with sepsis. CONCLUSION: This study will provide reliable evidence for the application of alanyl glutamine in nutritional support therapy for patients with sepsis. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/VRZPJ.


Assuntos
Dipeptídeos/administração & dosagem , Apoio Nutricional/métodos , Sepse/terapia , APACHE , Proteína C-Reativa/análise , Resultados de Cuidados Críticos , Estado Terminal/terapia , Hemoglobinas/análise , Humanos , Imunoglobulinas/sangue , Metanálise como Assunto , Pré-Albumina/análise , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Sepse/sangue , Albumina Sérica/análise , Revisões Sistemáticas como Assunto , Resultado do Tratamento
2.
Vet Res ; 52(1): 22, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33588935

RESUMO

COVID-19 is a zoonotic disease caused by SARS-CoV-2. Infections of animals with SARS-CoV-2 have recently been reported, and an increase of severe lung pathologies in domestic dogs has also been detected by veterinarians in Spain. Therefore, further descriptions of the pathological processes in those animals that show symptoms similar to those described in humans affected by COVID-19 would be highly valuable. The potential for companion animals to contribute to the continued transmission and community spread of this known human-to-human disease is an urgent issue to be considered. Forty animals with pulmonary pathologies were studied by chest X-ray, ultrasound analysis, and computed tomography. Nasopharyngeal and rectal swabs were analyzed to detect canine pathogens, including SARS-CoV-2. An additional twenty healthy dogs living in SARS-CoV-2-positive households were included. Immunoglobulin detection by several immunoassays was performed. Our findings show that sick dogs presented severe alveolar or interstitial patterns with pulmonary opacity, parenchymal abnormalities, and bilateral lesions. The forty sick dogs were negative for SARS-CoV-2 but Mycoplasma spp. was detected in 26 of 33 dogs. Five healthy and one pathological dog presented IgG against SARS-CoV-2. Here we report that despite detecting dogs with α-SARS-CoV-2 IgG, we never obtained a positive RT-qPCR for SARS-SoV-2, not even in dogs with severe pulmonary disease; suggesting that even in the case of canine infection, transmission would be unlikely. Moreover, dogs living in COVID-19-positive households could have been more highly exposed to infection with SARS-CoV-2.


Assuntos
/veterinária , Doenças do Cão/transmissão , Imunoglobulinas/sangue , Zoonoses/transmissão , Animais , /virologia , Doenças do Cão/virologia , Cães , Feminino , Imunidade Humoral , Masculino , Espanha , Zoonoses/virologia
3.
BMC Infect Dis ; 21(1): 38, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413180

RESUMO

BACKGROUND: Chronic mucocutaneous candidiasis (CMC) is the most common clinical symptom of singer transducer and signal transducer and activator of transcription 1 (STAT1) gain-of-function (GOF) mutations. Bronchiectasis is a chronic lung disease that is characterized by permanent bronchiectasis, causing cough, expectoration, and even haemoptysis. The underlying pathogeny is not yet clear. Immunoglobulin (Ig) A is derived from memory B cells and correlates with immune-related diseases. STAT1 is closely associated with signal transmission and immune regulation. CASE PRESENTATION: We report a 17-year-old male patient carrying a GOF mutation in STAT1. The variant led to CMC, bronchiectasis, and elevated serum IgA levels, as well as stunting. Whole-exome sequencing (WES) revealed a c.986C>G (p.P329R) heterozygous mutation in the STAT1 gene. CONCLUSION: Further Sanger sequencing analysis of STAT1 in the patient and his parents showed that the patient harboured a de novo mutation.


Assuntos
Bronquiectasia/genética , Candidíase Mucocutânea Crônica/genética , Transtornos do Crescimento/genética , Fator de Transcrição STAT1/genética , Adolescente , Linfócitos B/imunologia , Bronquiectasia/imunologia , Candidíase Mucocutânea Crônica/diagnóstico , Candidíase Mucocutânea Crônica/imunologia , Mutação com Ganho de Função , Heterozigoto , Humanos , Imunoglobulina A/sangue , Imunoglobulinas/sangue , Imunoglobulinas/genética , Masculino , Sequenciamento Completo do Exoma
4.
Ecotoxicol Environ Saf ; 210: 111825, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33412284

RESUMO

To explore the effect of florfenicol (FFC) combined with Salvia miltiorrhiza polysaccharide (SMPs) on immune function of Broilers. One hundred and twenty-one-day-old chicks were chosen and divided into 6 groups. The group A received standard basal diet only, the group B received a basal diet with FFC (0.15 g/L diet), and the group C, D, E received a basal diet with FFC (0.15 g/L diet) and SMPs (1.25 g/L, 2.5 g/L, 5 g/L diet),the group F received a basal diet with SMPs (5 g/L diet). FFC can significantly inhibit the growth performance of broilers, but has no significant damage to the immune function of broilers. The combination of FFC and SMPs can improve the growth performance of broilers, increase the number of leukocyte subtypes in blood (P < 0.05), increase the number of Newcastle disease (ND) and avian influenza (AI) antibodies in blood, the number of immunoglobulins, and the content of cytokines (P < 0.05). In addition, it significantly improve the lymphocyte conversion rate of broiler peripheral blood (P < 0.05). So that, synergistic use of FFC and SMPs can enhance immune responses in Broilers.


Assuntos
Antibacterianos/farmacologia , Galinhas/imunologia , Polissacarídeos/farmacologia , Salvia miltiorrhiza , Tianfenicol/análogos & derivados , Ração Animal , Animais , Anticorpos Antivirais/sangue , Galinhas/sangue , Galinhas/crescimento & desenvolvimento , Citocinas/sangue , Dieta , Suplementos Nutricionais , Humanos , Imunidade/efeitos dos fármacos , Imunoglobulinas/sangue , Influenza Humana/imunologia , Leucócitos/efeitos dos fármacos , Vírus da Doença de Newcastle/imunologia , Tianfenicol/farmacologia
5.
Methods Mol Biol ; 2223: 49-65, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33226586

RESUMO

Egg allergy is one of the most common food allergies in children, being the most important allergenic proteins found in the egg white (EW). Allergy to EW shows a complex phenotype that involves a multifaceted reaction that can only be assessed in vivo. Although other routes of sensitization have been described, oral exposure to food antigens is one of the most suitable in humans. In mice, oral administration of allergenic proteins results in the development of tolerance, and the use of adjuvants, such as cholera toxin (CT), is required to promote Th2-biased immune responses over tolerogenic responses. In this regard, among the mouse strains that readily display Th2 responses, Balb/c has been widely used. Here, we describe a frequently used protocol of oral EW sensitization by using CT as an adjuvant and we explain in detail the methods that we have developed to analyze the sensitizing and eliciting capacity of EW proteins including evaluation of signs, measurement of serum levels of specific immunoglobulins, mast cell degranulation, cytokine secretion profile of allergen-reactive T cells, phenotyping of mesenteric lymph node- and spleen-derived dendritic and T cells by flow cytometry, and quantification of intestinal gene expression.


Assuntos
Células Dendríticas/efeitos dos fármacos , Modelos Animais de Doenças , Hipersensibilidade a Ovo/imunologia , Clara de Ovo/química , Imunofenotipagem/métodos , Células Th2/efeitos dos fármacos , Adjuvantes Imunológicos/administração & dosagem , Administração Oral , Animais , Biomarcadores/metabolismo , Quimiocina CCL2/genética , Quimiocina CCL2/imunologia , Galinhas , Toxina da Cólera/administração & dosagem , Células Dendríticas/citologia , Células Dendríticas/imunologia , Hipersensibilidade a Ovo/sangue , Hipersensibilidade a Ovo/genética , Hipersensibilidade a Ovo/patologia , Feminino , Citometria de Fluxo , Expressão Gênica , Humanos , Imunoglobulinas/sangue , Imunoglobulinas/classificação , Imunoglobulinas/imunologia , Interleucinas/genética , Interleucinas/imunologia , Linfonodos/citologia , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Baço/citologia , Baço/efeitos dos fármacos , Baço/imunologia , Células Th2/citologia , Células Th2/imunologia
6.
Allergol. immunopatol ; 48(6): 612-618, nov.-dic. 2020.
Artigo em Inglês | IBECS | ID: ibc-199250

RESUMO

BACKGROUND: The chemical modification of allergens with glutaraldehyde improves safety while maintaining clinical efficacy, which permits the administration of higher doses of immunotherapy, reducing the risk of adverse reactions. The aim of this study is to evaluate the immunogenic capacity of a new cat dander polymer by immunizing mice and quantifying immunoglobulins in serum, in comparison with the non-modified allergen. METHODS: The study consists of the immunization of three mice groups with the polymerized and the native extract, together with a negative control group. The immunoglobulin levels in serum have been measured by indirect ELISA. By means of the non-parametric Mann-Whitney U test, it was determined if there were significant differences in the values of specific antibodies between groups. RESULTS: The group immunized with the allergoid showed significantly higher specific IgG and IgG1 values to dander allergens and specific IgG to the major allergen Fel d 1, while there were no significant changes in IgG2a and IgE values. These results could be due to a higher immunization dose. The vaccine formulation was based on the optimal defined dose for clinical efficacy of allergen immunotherapy. CONCLUSIONS: This preclinical study carried out with the present assay has established that the allergoid of cat dander extract, as designed for its optimal use in allergen immunotherapy, produces a higher specific IgG than the native extract, in addition to showing significantly higher specific IgG1 levels, evidencing a greater effectiveness in immunization


No disponible


Assuntos
Animais , Feminino , Gatos , Camundongos , Imunogenicidade da Vacina/imunologia , Dessensibilização Imunológica/métodos , Alérgenos/imunologia , Gatos/imunologia , Hipersensibilidade/prevenção & controle , Imunoglobulinas/sangue , Ensaio de Imunoadsorção Enzimática , Reprodutibilidade dos Testes , Valores de Referência , Avaliação Pré-Clínica de Medicamentos , Glicoproteínas/imunologia , Hipersensibilidade/imunologia
7.
Allergol. immunopatol ; 48(6): 675-685, nov.-dic. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-199258

RESUMO

INTRODUCTION AND OBJECTIVES: Common variable immunodeficiency (CVID) is one of the most prevalent forms of primary immunodeficiency characterized by hypogammaglobinemia. Its heterogeneous clinical features include recurrent respiratory tract infections and other complications such as gastrointestinal, autoimmunity, and lymphoproliferative disorders. The aim of this article is to evaluate the general characteristics of CVID patients. MATERIALS AND METHODS: Clinical and immunological features of 44 CVID patients were evaluated retrospectively with long-term follow-up. Patients who participated in the study were diagnosed according to the criteria of the European Society for Immunodeficiency Diseases (ESID). RESULTS: The median age at onset of symptoms was 2.75 years (range 6 months to 17 years), and the median age at diagnosis was 7.75 years (range 4-20 years). The average delay in diagnosis was 4.6 years (range 1-14 years). Positive family history was 18.2%. Before treatment, patients' median total serum IgG was 271.5mg/dL, median IgA was 7.5mg/dL, and median IgM was 21mg/dL. Infections were the most common clinical manifestation, and 63.6% of patients presented with sinopulmonary infection as the first manifestation. Bronchiectasis developed in 23 CVID subjects, while bronchiectasis was detected prior to CVID diagnosis in eight patients. All patients received immunoglobulin replacement therapy, and one patient died because of granulomatous lymphocytic interstitial lung disease (GLILD). CONCLUSIONS: CVID is a heterogeneous group of immunologic disorders with unknown etiology. There are significant differences in the clinical presentation and prevalence of CVID-related complications among countries. Local guidelines for diagnosis and clinical follow-up are needed


No disponible


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Imunodeficiência de Variável Comum/epidemiologia , Imunodeficiência de Variável Comum/patologia , Imunodeficiência de Variável Comum/sangue , Estudos Retrospectivos , Fatores Etários , Estatísticas não Paramétricas , Seguimentos , Imunoglobulinas/sangue , Linfócitos , Turquia/epidemiologia
8.
Medicine (Baltimore) ; 99(45): e22390, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33157914

RESUMO

Community-acquired pneumonia (CAP) is a worldwide cause of morbidity and mortality. Immunoglobulins (Igs) and B cells quantification studies in CAP are few and show discrepancies. Serum IgA acts as a powerful natural anti-inflammatory factor, but its role in the CAP has not yet been defined. The highly sensitive xMAP Luminex technique allows better immunoglobulins quantification. The aim of this study was to analyze the relation between clinical severity and circulating Igs and B cells in adults with CAP.Igs (M, A, G1, G2, G3, and G4) and B cells were quantified in peripheral blood of 190 Chilean patients ≥18 years old hospitalized for CAP and in 21 adults without respiratory disease, using xMAP Luminex and flow cytometry, respectively. Clinical history was recorded and PSI and CURB-65 scores were calculated for evaluation of clinical severity.The total IgM, IgG2 and total IgG levels were lower in CAP than in asymptomatic adults (P < .05). No significant differences of Igs levels were found between patients classified as severe and mild by PSI and CURB-65 scores. Fatal cases had higher levels of IgA (P < .05). No differences in CD19 B cells frequency was found between CAP and asymptomatic adults (P = .40). In PSI severe cases, CD19 B cells were significantly lower than in mild cases (P = .008). No differences were found in CURB-65 severe and mild groups (P = .11). In fatal cases (11/82) group, CD19 B cells frequency was lower than in 71 survivors (P = .2). No differences in memory B lymphocytes were detected between asymptomatic and CAP adults, severe and mild patients, survivors and fatal cases (P > .05).Serum IgA levels were significantly higher in fatal CAP cases, raising it as a potential biomarker for severe disease considering its relatively universal availability. In PSI severe patients, B cells showed lower levels and could have a role on its physiopathology. Finding new markers rooted in physiopathology could improve the possibility of scoring severe CAP cases. Luminex technology showed promising quantification serum Igs.


Assuntos
Linfócitos B/imunologia , Infecções Comunitárias Adquiridas/imunologia , Imunoglobulinas/sangue , Pneumonia/imunologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Contagem de Células , Chile , Estudos Transversais , Feminino , Citometria de Fluxo , Humanos , Testes Imunológicos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
9.
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
10.
Pediatr Infect Dis J ; 39(11): e366-e367, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33021596

RESUMO

With recent reports showing clinical and laboratory overlap of multisystem inflammatory syndrome in children and Kawasaki disease (KD), we addressed the hypothesis that cross coronavirus humoral immunity leads to a parallel postinfectious phenomenon explaining similar pathologic findings in KD and multisystem inflammatory syndrome in children. We demonstrated no cross-reactivity in children with KD but observed some nonspecific interactions postintravenous immunoglobulin infusion.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Imunoglobulinas/imunologia , Síndrome de Linfonodos Mucocutâneos/imunologia , Pneumonia Viral/imunologia , Proteínas Virais/imunologia , Criança , Infecções por Coronavirus/sangue , Infecções por Coronavirus/virologia , Reações Cruzadas/imunologia , Humanos , Imunidade Humoral , Imunoglobulinas/sangue , Síndrome de Linfonodos Mucocutâneos/sangue , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/virologia
11.
J Med Life ; 13(3): 371-377, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072210

RESUMO

The study of the incidence of cryoglobulinemia is relevant in patients with an intestinal anastomotic leak. This study aims to determine a laboratory marker of the risk of small intestine anastomotic leak. The study was based on 96 patients who were subjected to resections of segments of the small intestine with the formation of intestinal anastomoses at the State Institution "Zaytsev V.T. Institute of General and Urgent Surgery of National Academy of Medical Sciences of Ukraine". Of all the operated patients, there were 55.2% women and 44.8% men. Of the 96 patients examined, cryoglobulinemia was detected in the majority - 62.5% of patients, of which 4 were later proved to have inactive hepatitis C; the remaining 38.5% had no cryoglobulinemia. According to the existing theory of the autoimmune mechanism of postoperative surgical complications formation, the revealed decrease in the level of cryoglobulins on the second day could be related to their fixation in the microcirculatory bed and the development of immunocomplex inflammation. While the increase in the content of cryoglobulins in serum on the third day can be caused by their entry into the circulatory bed from deposition or fixation sites and the development of a secondary immune response. In patients with intestinal anastomosis failure after resection of intestinal segments, cryoglobulinemia rates increased more than 80 mg/l; this indicator could be used as a marker of postoperative complications.


Assuntos
Crioglobulinas/análise , Procedimentos Cirúrgicos do Sistema Digestório , Intestino Delgado/cirurgia , Anastomose Cirúrgica/efeitos adversos , Crioglobulinemia/sangue , Crioglobulinemia/imunologia , Feminino , Humanos , Imunoglobulinas/sangue , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Fagocitose , Ucrânia
12.
BMJ Open ; 10(10): e040036, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33028562

RESUMO

INTRODUCTION: As of 30 April 2020, the novel betacoronavirus SARS-CoV-2 had infected more than 3 172 000 individuals, killing over 224 000 people and spreading to more than 200 countries. Italy was the most affected country in Europe and the third most affected in the world in terms of the number of cases. Therefore, the aims of this study are: (1) to estimate the prevalence of asymptomatic SARS-CoV-2-positive individuals among the general population of Verona; (2) to assess the accuracy (sensitivity, specificity and predictive values) of an ELISA serological test for the screening of SARS-CoV-2. METHODS AND ANALYSIS: The study will be carried out on a random sample of subjects aged at least 10 years from the general population of Verona. Participants will undergo the measurement of vital parameters (oxygen saturation measured by oximeter, respiratory rate and body temperature detected by laser thermometer), the administration of a COVID-19-related symptoms questionnaire, the collection of a blood sample and a nasopharyngeal swab. Our evaluation will include the statistical technique of Latent Class Analysis, which will be the basis for the estimation of prevalence. ETHICS AND DISSEMINATION: The study protocol has been approved by the Ethics Committee of Verona and Rovigo provinces on 15 April 2020 (internal protocol number 2641CESC). The study results will be submitted for publication in international, peer-reviewed journals and the complete dataset will be deposited in a public repository. Most relevant data will be made available to policy-makers as well as disseminated to stakeholders and to the community.


Assuntos
Infecções Assintomáticas/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Programas de Rastreamento/métodos , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Testes Sorológicos/métodos , Adulto , Anticorpos Antivirais/sangue , Betacoronavirus , Criança , Protocolos Clínicos , Infecções por Coronavirus/sangue , Infecções por Coronavirus/virologia , Estudos Transversais , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Imunoglobulinas/sangue , Itália , Pneumonia Viral/sangue , Pneumonia Viral/virologia , Prevalência , Projetos de Pesquisa , Sensibilidade e Especificidade , Síndrome Respiratória Aguda Grave
13.
PLoS One ; 15(9): e0239295, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32941525

RESUMO

Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal cancer, particularly in ulcerative colitis (UC) when the majority of colon epithelial cells may be exposed to inflammation-associated mutagenesis. In addition to mutagenesis generated by oxidative stress, inflammation can induce activation-induced cytidine deaminase (Aicda), a mutator enzyme in the APOBEC family, within colon epithelial cells. This study tested the hypothesis that deletion of the Aicda gene could protect against the development of inflammation-associated colorectal cancers, using a model of UC-like colitis in "T/I" mice deficient in TNF and IL10. Results showed that T/I mice that were additionally Aicda-deficient ("TIA" mice) spontaneously developed moderate to severe UC-like colitis soon after weaning, with histologic features and colon inflammation severity scores similar those in T/I mice. Although the mean survival of TIA mice was decreased compared to T/I mice, multivariable analysis that adjusted for age when neoplasia was ascertained showed a decreased numbers of neoplastic colorectal lesions in TIA mice, with a trend toward decreased incidence of neoplasia. Aicda deficiency increased serum IL1α and slightly decreased IL12p40 and M-CSF, as compared with T/I mice, and led to undetectable levels of IgA, IgG1, IgG2a, IgG2b, and IgG3. Taken together, these studies show that Aicda deficiency can decrease the number of neoplastic lesions but is not sufficient to prevent the risk of inflammation-associated colorectal neoplasia in the setting of severe UC-like inflammation. The TIA model may also be useful for assessing the roles of antibody class-switch recombination deficiency and somatic hypermutation on regulation of microbiota and inflammation in the small intestine and colon, as well as the pathogenesis of colitis associated with hyper-IgM syndrome in humans. Further studies will be required to determine the mechanisms that drive early mortality in TIA mice.


Assuntos
Colite Ulcerativa/genética , Neoplasias Colorretais/genética , Citidina Desaminase/genética , Animais , Colite Ulcerativa/complicações , Colite Ulcerativa/patologia , Colo/metabolismo , Colo/patologia , Neoplasias Colorretais/etiologia , Citidina Desaminase/deficiência , Feminino , Deleção de Genes , Imunoglobulinas/sangue , Interleucina-1/sangue , Interleucina-10/genética , Interleucina-12/sangue , Fator Estimulador de Colônias de Macrófagos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/genética
14.
Science ; 369(6508): 1210-1220, 2020 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-32788292

RESUMO

Coronavirus disease 2019 (COVID-19) represents a global crisis, yet major knowledge gaps remain about human immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed immune responses in 76 COVID-19 patients and 69 healthy individuals from Hong Kong and Atlanta, Georgia, United States. In the peripheral blood mononuclear cells (PBMCs) of COVID-19 patients, we observed reduced expression of human leukocyte antigen class DR (HLA-DR) and proinflammatory cytokines by myeloid cells as well as impaired mammalian target of rapamycin (mTOR) signaling and interferon-α (IFN-α) production by plasmacytoid dendritic cells. By contrast, we detected enhanced plasma levels of inflammatory mediators-including EN-RAGE, TNFSF14, and oncostatin M-which correlated with disease severity and increased bacterial products in plasma. Single-cell transcriptomics revealed a lack of type I IFNs, reduced HLA-DR in the myeloid cells of patients with severe COVID-19, and transient expression of IFN-stimulated genes. This was consistent with bulk PBMC transcriptomics and transient, low IFN-α levels in plasma during infection. These results reveal mechanisms and potential therapeutic targets for COVID-19.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Pneumonia Viral/imunologia , Citocinas/sangue , DNA Bacteriano/sangue , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Feminino , Citometria de Fluxo , Antígenos HLA-DR/análise , Humanos , Imunidade , Imunidade Inata , Imunoglobulinas/sangue , Imunoglobulinas/imunologia , Mediadores da Inflamação/sangue , Interferon Tipo I/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Lipopolissacarídeos/sangue , Masculino , Células Mieloides/imunologia , Células Mieloides/metabolismo , Pandemias , Transdução de Sinais , Análise de Célula Única , Biologia de Sistemas , Serina-Treonina Quinases TOR/metabolismo , Transcrição Genética , Transcriptoma
15.
J Environ Pathol Toxicol Oncol ; 39(2): 137-147, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32749123

RESUMO

Lung carcinogenesis is one of the main sources of cancer-related mortality globally and it is estimated that nearly 1 million people die from it every year. The 5-year survival rate of lung carcinogenesis is reported at just 15%. The aim of the current research was to investigate the immunomodulatory effect of eriocitrin against benzo(a)pyrene [B(a) P]-induced lung tumorigenesis in Swiss albino mice. The lung sarcoma was provoked through oral gavage of B(a)P (50 mg/kg body weight) two times/week for four weeks. CEA, lung weight, lipid peroxidation (LPO), body weight, immuno-globulin (IgG, IgA, and IgM), tumor incidence, serum marker enzymes (LDH, AHH, λ-GT, and 5'-NTs), hematological counts (leucocytes, lymphocytes, neutrophils, absolute numbers of lymphocytes and neutrophils), antioxidants (SOD and CAT), inflammatory modulators (IL-1ß, IL-6, and TNF-α), immune complexes (avidity index, phagocyte index, NBT reduction, and SIC) and histopathological changes were analyzed. Moreover, the status of apoptosis proteins (Bax, caspase-9, and caspase-3) and cell proliferative protein (cyclin D1 and cyclin A) expression was determined by Western blot and PCNA by immunohistochemical analysis. B(a)P-challenged cancer-bearing mice exhibited augmented levels of lipid peroxidation, tumor incidence, lung weight, CEA, serum marker enzymes, IgA, SIC, cell proliferative markers, and inflammatory cytokines with concurrent decrease in body weight, antioxidant levels, hematological counts, immunoglobulins, immune complexes, and apoptotic protein expression. The eriocitrin treatments caused significant reversion of all these marker to previous levels. Overall, the results propose the immunomodulatory prospective of eriocitrin against B(a) P-induced lung carcinogenesis on Swiss albino mice.


Assuntos
Flavanonas/farmacologia , Fatores Imunológicos/farmacologia , Neoplasias Pulmonares/prevenção & controle , Animais , Anticarcinógenos/farmacologia , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Benzo(a)pireno/toxicidade , Peso Corporal/efeitos dos fármacos , Citocinas/metabolismo , Imunoglobulinas/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Fagócitos/efeitos dos fármacos
16.
Ecotoxicol Environ Saf ; 201: 110824, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32544747

RESUMO

The aim of the study was to investigate the effects of sublethal concentrations (0.3, 0.6 and 1.2 mg L-1) of the herbicide Ronstar on the hematology and some immune parameters in Clarias gariepinus juvenile (mean weight and length 58.72 ± 2.46 g and 27.60 ± 1.62 cm, respectively). The hematological and some immune parameters were studied for 21 days in a static renewal bioassay system in which the water and the herbicide were changed daily. The erythrocyte count, hemoglobin concentration (Hb), and packed cell volume (PCV) were significantly (p < 0.05) reduced in the treatment groups. When compared with the control, there were significant (p < 0.05) leucocytosis, lymphocytosis, neutropenia and monocytopenia in the treatment groups. Both the mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) were reduced ((p < 0.05) in the Ronstar-exposed fish. The result showed that the treated fish suffered hypochromic microcytic anemia. The total immunoglobulin and phagocytic indices (phagocytic capacity and phagocytic index) were significantly (p < 0.05) reduced in the treatment groups. while the respiratory burst was significantly (p < 0.05) increased in the treatment groups. The result showed that exposure to Ronstar had adverse effects on the hematology and immunocompetency of the fish.


Assuntos
Peixes-Gato , Herbicidas/toxicidade , Imunoglobulinas/sangue , Oxidiazóis/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Peixes-Gato/sangue , Peixes-Gato/imunologia , Relação Dose-Resposta a Droga , Contagem de Eritrócitos , Índices de Eritrócitos/efeitos dos fármacos , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Hematócrito , Hemoglobinas/análise , Fagócitos/citologia , Fagócitos/efeitos dos fármacos
17.
Ann Hematol ; 99(8): 1907-1915, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32444892

RESUMO

Despite significant progress made in the treatment of patients with multiple myeloma (MM) in the last decade, for patients with early relapse or rapidly progressing high-risk disease, allogeneic hematopoietic stem cell transplantation (SCT) might be an option leading to long-term survival. Here, we retrospectively analyzed the outcomes of 90 MM patients who received allogeneic SCT in our center between 1999 and 2017. We specifically assessed the association of impaired humoral immune reconstitution, referred to as immunoparesis, and post-transplant survival. Sixty-four patients received allogeneic SCT in relapse following 2-7 lines of therapy; 26 patients received upfront tandem autologous-allogeneic SCT. With a median follow-up of 76 months, OS and PFS were 52.6% (95% CI 42.9-64.3) and 36.4% (95% CI 27.6-47.9) at 2 years and 38.6% (95% CI 29.2-51.1) and 25.3% (95% CI 17.5-36.4) at 5 years, respectively. Receiving more than two therapy lines prior to transplantation was an independent risk factor for OS (HR 3.68, 95% CI 2.02-6.70) and PFS (HR 3.69, 95% CI 2.09-6.50). In a landmark analysis at day 200, prolonged immunoparesis was associated with reduced OS (HR 3.22, 95% CI 1.14-9.11). Allogeneic stem cell transplantation offers an additional treatment element that may lead to long-term remission in selected patients with poor prognosis, probably exploiting graft-versus-myeloma effects. Immunoparesis could potentially serve as an indicator for impaired survival following allogeneic transplantation, an observation to be further studied prospectively.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Imunoglobulinas/sangue , Mieloma Múltiplo , Adulto , Idoso , Aloenxertos , Autoenxertos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/sangue , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
19.
Artigo em Inglês | MEDLINE | ID: mdl-32308113

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are typical pollutants and may be alkylated and oxygenated to form alkyl-PAHs and oxygenated-PAHs (oxy-PAHs), respectively. Takifugu obscurus is an important anadromous fish species and displays a high risk of being exposed to PAHs-contaminated areas. In the present study, the effects of acute exposure to 44.29 µg L-1 9,10-phenanthrenequione (9,10-PQ), retene and phenanthrene (Phe) on T. obscurus liver histology, antioxidant enzymes and immune indices were compared. After exposure to these three compounds, histological sections showed damages of hepatocyte, and the activities of alanine and aspartate aminotransferase increased in plasma, indicating direct hepatic toxicity. Hepatic malondialdehyde (MDA) content increased, but superoxide dismutase (SOD) and catalase (CAT) activities decreased in response to treatments with Phe, retene and 9,10-PQ. These results revealed peroxidative effects on T. obscurus hepatocytes. In addition, total immunoglobulin content and lysozyme activity in plasma increased in treatments with Phe, retene and 9,10-PQ, which might be resulted from the damaged liver cells and the subsequently hepatic inflammation. Besides, the changes were more severe in treatment with 9,10-PQ than those with Phe and retene, demonstrating higher toxicity of 9,10-PQ than the other two compounds. Overall, the present study posed a high environmental risk of PAH derivatives to aquatic ecosystems.


Assuntos
Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenantrenos/toxicidade , Takifugu , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Ecossistema , Imunoglobulinas/sangue , Fígado/enzimologia , Fígado/imunologia , Fígado/patologia , Malondialdeído/metabolismo
20.
J Dairy Sci ; 103(6): 5525-5531, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32253037

RESUMO

It is well established that intravenous administration of lipopolysaccharides (LPS)-cell wall components from gram-negative bacteria-induce acute inflammatory responses in dairy calves, but the effect of oral administration of LPS to dairy calves is currently unknown. To evaluate the effects of oral administration of LPS derived from Escherichia coli (serotype O111:B4) on innate immune responses in milk-fed Holstein calves, 20 visually healthy calves (34 ± 1 d) received 4 L of milk with LPS (12 µg/kg body weight; n = 10; LPS) or without LPS (n = 10; control) at the morning feeding. Samples were collected at 0.5 h before the morning feeding and at 3, 6, 24, 48, 72, and 168 h after the morning feeding to measure rectal temperature and heart rate, as well as plasma-negative and plasma-positive acute phase proteins (i.e., haptoglobin, serum amyloid A, albumin, total protein, and fibrinogen) and immunoglobulin concentrations (IgG, IgM, and IgA). None of these measurements was affected by the oral administration of LPS. Oral administration of LPS at 12 µg/kg of body weight did not induce an acute inflammatory response in visually healthy milk-fed Holstein calves when administered in milk.


Assuntos
Bovinos/imunologia , Escherichia coli/química , Imunidade Inata/efeitos dos fármacos , Lipopolissacarídeos/imunologia , Proteínas da Fase Aguda/análise , Proteínas da Fase Aguda/efeitos dos fármacos , Administração Oral , Animais , Peso Corporal , Imunoglobulinas/sangue , Lipopolissacarídeos/administração & dosagem , Masculino , Leite/metabolismo , Sorogrupo
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