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  1. Article ; Online: Remodeling of the Immune Response With Aging

    Lucas Leite Cunha / Sandro Felix Perazzio / Jamil Azzi / Paolo Cravedi / Leonardo Vidal Riella

    Frontiers in Immunology, Vol

    Immunosenescence and Its Potential Impact on COVID-19 Immune Response

    2020  Volume 11

    Abstract: Elderly individuals are the most susceptible to an aggressive form of coronavirus disease (COVID-19), caused by SARS-CoV-2. The remodeling of immune response that is observed among the elderly could explain, at least in part, the age gradient in ... ...

    Abstract Elderly individuals are the most susceptible to an aggressive form of coronavirus disease (COVID-19), caused by SARS-CoV-2. The remodeling of immune response that is observed among the elderly could explain, at least in part, the age gradient in lethality of COVID-19. In this review, we will discuss the phenomenon of immunosenescence, which entails changes that occur in both innate and adaptive immunity with aging. Furthermore, we will discuss inflamm-aging, a low-grade inflammatory state triggered by continuous antigenic stimulation, which may ultimately increase all-cause mortality. In general, the elderly are less capable of responding to neo-antigens, because of lower naïve T cell frequency. Furthermore, they have an expansion of memory T cells with a shrinkage of the T cell diversity repertoire. When infected by SARS-CoV-2, young people present with a milder disease as they frequently clear the virus through an efficient adaptive immune response. Indeed, antibody-secreting cells and follicular helper T cells are thought to be effectively activated in young patients that present a favorable prognosis. In contrast, the elderly are more prone to an uncontrolled activation of innate immune response that leads to cytokine release syndrome and tissue damage. The failure to trigger an effective adaptive immune response in combination with a higher pro-inflammatory tonus may explain why the elderly do not appropriately control viral replication and the potential clinical consequences triggered by a cytokine storm, endothelial injury, and disseminated organ injury. Enhancing the efficacy of the adaptive immune response may be an important issue both for infection resolution as well as for the appropriate generation of immunity upon vaccination, while inhibiting inflamm-aging will likely emerge as a potential complementary therapeutic approach in the management of patients with severe COVID-19.
    Keywords immunosenescence ; inflammaging ; SARS-CoV-2 ; COVID-19 ; immunopathogenesis ; Immunologic diseases. Allergy ; RC581-607 ; covid19
    Subject code 616 ; 610
    Language English
    Publishing date 2020-08-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Mild and moderate Mannose Binding Lectin deficiency are associated with systemic lupus erythematosus and lupus nephritis in Brazilian patients

    Sandro Félix Perazzio / Neusa Pereira da Silva / Magda Carneiro-Sampaio / Luis Eduardo Coelho Andrade

    Revista Brasileira de Reumatologia, Vol 56, Iss 3, Pp 220-

    2016  Volume 227

    Abstract: Abstract Objective The potential association of mannose binding lectin (MBL) deficiency and systemic lupus erythematosus (SLE) has been investigated in several studies, but results have been mixed. One explanation for the conflicting results could be ... ...

    Abstract Abstract Objective The potential association of mannose binding lectin (MBL) deficiency and systemic lupus erythematosus (SLE) has been investigated in several studies, but results have been mixed. One explanation for the conflicting results could be differences in ethnic background of study subjects. In this study we investigated the association of MBL deficiency and SLE in a large cohort of Brazilian SLE patients and controls. Methods Serum MBL and Complement levels were determined for 286 Brazilian adult SLE patients and 301 healthy Brazilian adults as controls. MBL deficiency was classified as mild (<1000 and ≥500 µg/L), moderate (<500 and ≥100 µg/L) or severe (<100 µg/L). Results SLE patients presented higher frequency of mild and moderate MBL deficiency compared to controls. SLE patients with MBL deficiency presented higher frequency of lupus nephritis compared to those without MBL deficiency. MBL deficiency was not associated with any other clinical manifestation, use of immunosuppressant therapy, disease activity, disease severity serum or Complement levels. Conclusion This study shows that an association between MBL deficiency and SLE does exist in the Brazilian population. We also found an association between MBL deficiency and lupus nephritis. These findings support the hypothesis that MBL deficiency contributes to the development of SLE and lupus nephritis.
    Keywords Deficiência de LLM ; Lúpus eritematoso sistêmico ; Imunodeficiência ; Nefrite lúpica ; Diseases of the musculoskeletal system ; RC925-935 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2016-06-01T00:00:00Z
    Publisher Sociedade Brasileira de Reumatologia
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Parental segregation study reveals rare benign and likely benign variants in a Brazilian cohort of rare diseases

    Caio Robledo D.’Angioli Costa Quaio / Jose Ricardo Magliocco Ceroni / Murilo Castro Cervato / Helena Strelow Thurow / Caroline Monaco Moreira / Ana Carolina Gomes Trindade / Cintia Reys Furuzawa / Rafaela Rogerio Floriano de Souza / Sandro Felix Perazzio / Aurelio Pimenta Dutra / Christine Hsiaoyun Chung / Chong Ae Kim

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 9

    Abstract: Abstract Genomic studies may generate massive amounts of data, bringing interpretation challenges. Efforts for the differentiation of benign and pathogenic variants gain importance. In this article, we used segregation analysis and other molecular data ... ...

    Abstract Abstract Genomic studies may generate massive amounts of data, bringing interpretation challenges. Efforts for the differentiation of benign and pathogenic variants gain importance. In this article, we used segregation analysis and other molecular data to reclassify to benign or likely benign several rare clinically curated variants of autosomal dominant inheritance from a cohort of 500 Brazilian patients with rare diseases. This study included only symptomatic patients who had undergone molecular investigation with exome sequencing for suspected diseases of genetic etiology. Variants clinically suspected as the causative etiology and harbored by genes associated with highly-penetrant conditions of autosomal dominant inheritance underwent Sanger confirmation in the proband and inheritance pattern determination because a “de novo” event was expected. Among all 327 variants studied, 321 variants were inherited from asymptomatic parents. Considering segregation analysis, we have reclassified 51 rare variants as benign and 211 as likely benign. In our study, the inheritance of a highly penetrant variant expected to be de novo for pathogenicity assumption was considered as a non-segregation and, therefore, a key step for benign or likely benign classification. Studies like ours may help to identify rare benign variants and improve the correct interpretation of genetic findings.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Associação de imunodeficiência primária com lúpus eritematoso sistêmico

    Paolo Ruggero Errante / Sandro Félix Perazzio / Josias Brito Frazão / Neusa Pereira da Silva / Luis Eduardo Coelho Andrade

    Revista Brasileira de Reumatologia, Vol 56, Iss 1, Pp 58-

    revisão da literatura e as lições aprendidas pela Divisão de Reumatologia de um hospital universitário terciário em São Paulo

    2016  Volume 68

    Abstract: Resumo As imunodeficiências primárias (IDP) representam um grupo heterogêneo de doenças resultantes de defeitos hereditários no desenvolvimento, na maturação e na função normal de células do sistema imunológico; assim, tornam os indivíduos suscetíveis a ... ...

    Abstract Resumo As imunodeficiências primárias (IDP) representam um grupo heterogêneo de doenças resultantes de defeitos hereditários no desenvolvimento, na maturação e na função normal de células do sistema imunológico; assim, tornam os indivíduos suscetíveis a infecções recorrentes, alergia, autoimunidade e doenças malignas. Neste estudo retrospectivo descrevem-se doenças autoimunes (DAI), em especial o lúpus eritematoso sistêmico (LES), que surgiram associadas ao curso das IDP. Classicamente, a literatura descreve três grupos de IDP associadas ao LES: (1) deficiência de componentes da via do complemento, (2) defeitos na síntese de imunoglobulinas e (3) doença granulomatosa crônica (DGC). Na atualidade, outras IDP têm sido descritas como manifestações clínicas do LES, como a síndrome de Wiskott-Aldrich (WAS), a poliendocrinopatia autoimune-candidíase-distrofia ectodérmica (APECED), a síndrome linfoproliferativa autoimune (ALPS) e a linfocitopenia idiopática CD4+. Também são apresentados achados de uma coorte de adultos do ambulatório da Divisão de Reumatologia da Universidade Federal de São Paulo. As manifestações de IDP encontradas pelo nosso grupo de estudo foram consideradas leves em termos de gravidade de infecções e mortalidade no início da vida. Assim, é possível que alguns estados de imunodeficiência sejam compatíveis com a sobrevivência em relação à suscetibilidade infecciosa; no entanto, esses estados podem representar um fator de predisposição forte para o desenvolvimento de doenças imunológicas, como observado no LES.
    Keywords Doença autoimune ; Imunodeficiência primária ; Lúpus eritematoso sistêmico ; Deficiência de anticorpos ; Diseases of the musculoskeletal system ; RC925-935 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R
    Language Portuguese
    Publishing date 2016-02-01T00:00:00Z
    Publisher Sociedade Brasileira de Reumatologia
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Perception of usefulness of laboratory tests ordering by internal medicine residents in ambulatory setting

    Dimitria Doi / Romulo Ribeiro do Vale / Jean Michell Correia Monteiro / Glauco Cabral Marinho Plens / Mario Ferreira Junior / Luiz Augusto Marcondes Fonseca / Sandro Félix Perazzio / Bruno Adler Maccagnan Pinheiro Besen / Arnaldo Lichtenstein / Leandro Utino Taniguchi / Nairo Massakazu Sumita / Aline Pivetta Corá / Adriana Pasmanik Eisencraft / Alberto José da Silva Duarte

    PLoS ONE, Vol 16, Iss 5, p e

    A single-center prospective cohort study.

    2021  Volume 0250769

    Abstract: The demand for high value health care uncovered a steady trend in laboratory tests ordering and inappropriate testing practices. Residents' training in laboratory ordering practice provides an opportunity for quality improvement. We collected information ...

    Abstract The demand for high value health care uncovered a steady trend in laboratory tests ordering and inappropriate testing practices. Residents' training in laboratory ordering practice provides an opportunity for quality improvement. We collected information on demographics, the main reason for the appointment, preexisting medical conditions and presence of co-morbidities from first-visit patients to the internal medicine outpatient service of our university general hospital. We also collected information on all laboratory tests ordered by the attending medical residents. At a follow-up visit, we recorded residents' subjective perception on the usefulness of each ordered laboratory test for the purposes of diagnosis, prognosis, treatment or screening. We observed that 17.3% of all ordered tests had no perceived utility by the attending resident. Tests were usually ordered to exclude differential diagnoses (26.7%) and to help prognosis estimation (19.1%). Age and co-morbidity influenced the chosen category to legitimate usefulness of tests ordering. This study suggests that clinical objectives (diagnosis, prognosis, treatment or prevention) as well as personalization to age and previous health conditions should be considered before test ordering to allow a more appropriate laboratory tests ordering, but further studies are necessary to examine this framework beyond this medical training scenario.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Global DNA methylation pattern and correlation with complement system proteins in Brazilian patients with systemic lupus erythematosus

    Paolo Ruggero Errante / Sandro Félix Perazzio / Francisco Sandro Menezes Rodrigues / Renato Ribeiro Nogueira Ferraz / Afonso Caricati-Neto

    ConScientiae Saúde, Vol 13, Iss 4, Pp 516-

    2014  Volume 523

    Abstract: Introduction:Nucleic acid methylation may have major effects on gene expres-sion patterns and, by consequence, on the development of autoimmunity, likeSystemic Lupus Erythematosus (SLE).Objective:To investigate the pattern ofglobal DNA methylation in SLE ...

    Abstract Introduction:Nucleic acid methylation may have major effects on gene expres-sion patterns and, by consequence, on the development of autoimmunity, likeSystemic Lupus Erythematosus (SLE).Objective:To investigate the pattern ofglobal DNA methylation in SLE patients and compare this pattern with labora-tory parameters.Methods:Genomic DNA was isolated from SLE patients withnon-active disease (SLEDAI<6), SLE patients with active disease (SLEDAI>6),and healthy individuals. Global DNA methylation was evaluated by digestion ofgenomic DNA withHpaII andMspI and compared with laboratory parameters.Results and conclusion:A statistical difference in DNA global methylation wasobserved when SLE patients were compared to healthy individuals. A positivecorrelation was observed between the frequency of global methylation and C3and C4 serum levels for SLE patients with SLEDAI<6. These results suggestthat the relative amount of DNA methylation is increased in SLE patients, anddifferential methylation of genes related to the complement pathway alters geneexpression involved in autoimmune response in SLE patients.
    Keywords Diseases of the musculoskeletal system ; RC925-935 ; Sports medicine ; RC1200-1245
    Language Portuguese
    Publishing date 2014-01-01T00:00:00Z
    Publisher Universidade Nove de Julho
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Use and misuse of biomarkers and the role of D-dimer and C-reactive protein in the management of COVID-19

    Fabio Augusto Rodrigues Gonçalves / Bruno Adler Maccagnan Pinheiro Besen / Clarice Antunes de Lima / Aline Pivetta Corá / Antônio José Rodrigues Pereira / Sandro Félix Perazzio / Christiane Pereira Gouvea / Luiz Augusto Marcondes Fonseca / Evelinda Marramon Trindade / Nairo Massakazu Sumita / Alberto José da Silva Duarte / Arnaldo Lichtenstein / Eloisa Bonfa / Edivaldo M. Utiyama / Aluisio C. Segurado / Beatriz Perondi / Anna Miethke-Morais / Amanda C. Montal / Leila Harima /
    Solange R. G. Fusco / Marjorie F. Silva / Marcelo C. Rocha / Izabel Marcilio / Izabel Cristina Rios / Fabiane Yumi Ogihara Kawano / Maria Amélia de Jesus / Ésper George Kallas / Carolina Carmo / Clarice Tanaka / Heraldo Possolo de Souza / Julio F. M. Marchini / Carlos Carvalho / Juliana C. Ferreira / Anna Sara Shafferman Levin / Maura Salaroli Oliveira / Thaís Guimarães / Carolina dos Santos Lázari / Ester Sabino / Marcello M. C. Magri / Tarcisio E. P. Barros-Filho / Maria Cristina Peres Braido Francisco / Silvia F. Costa

    Clinics, Vol

    A post-hoc analysis of a prospective cohort study

    2021  Volume 76

    Abstract: OBJECTIVE: Coronavirus disease 2019 (COVID-19) is associated with high mortality among hospitalized patients and incurs high costs. Severe acute respiratory syndrome coronavirus 2 infection can trigger both inflammatory and thrombotic processes, and ... ...

    Abstract OBJECTIVE: Coronavirus disease 2019 (COVID-19) is associated with high mortality among hospitalized patients and incurs high costs. Severe acute respiratory syndrome coronavirus 2 infection can trigger both inflammatory and thrombotic processes, and these complications can lead to a poorer prognosis. This study aimed to evaluate the association and temporal trends of D-dimer and C-reactive protein (CRP) levels with the incidence of venous thromboembolism (VTE), hospital mortality, and costs among inpatients with COVID-19. METHODS: Data were extracted from electronic patient records and laboratory databases. Crude and adjusted associations for age, sex, number of comorbidities, Sequential Organ Failure Assessment score at admission, and D-dimer or CRP logistic regression models were used to evaluate associations. RESULTS: Between March and June 2020, COVID-19 was documented in 3,254 inpatients. The D-dimer level ≥4,000 ng/mL fibrinogen equivalent unit (FEU) mortality odds ratio (OR) was 4.48 (adjusted OR: 1.97). The CRP level ≥220 mg/dL OR for death was 7.73 (adjusted OR: 3.93). The D-dimer level ≥4,000 ng/mL FEU VTE OR was 3.96 (adjusted OR: 3.26). The CRP level ≥220 mg/dL OR for VTE was 2.71 (adjusted OR: 1.92). All these analyses were statistically significant (p<0.001). Stratified hospital costs demonstrated a dose-response pattern. Adjusted D-dimer and CRP levels were associated with higher mortality and doubled hospital costs. In the first week, elevated D-dimer levels predicted VTE occurrence and systemic inflammatory harm, while CRP was a hospital mortality predictor. CONCLUSION: D-dimer and CRP levels were associated with higher hospital mortality and a higher incidence of VTE. D-dimer was more strongly associated with VTE, although its discriminative ability was poor, while CRP was a stronger predictor of hospital mortality. Their use outside the usual indications should not be modified and should be discouraged.
    Keywords COVID-19 ; Biomarkers ; Cohort Studies ; Venous Thromboembolism ; Health Care Costs ; Medicine (General) ; R5-920
    Subject code 310
    Language English
    Publishing date 2021-12-01T00:00:00Z
    Publisher Elsevier España
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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