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LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina

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Agora exibindo 1 - 10 de 30
  • article 1 Citação(ões) na Scopus
    Social impact of disease parameters and damage accrual in adult Brazilian patients with childhood-onset Systemic Lupus Erythematosus
    (2022) TANIGAVA, Nicolas Y.; SAKAMOTO, Ana P.; FRANCO, Andre S.; BALBI, Gabriela G. M.; SALES, Lucas P.; AIKAWA, Nadia E.; TERRERI, Maria T.; PEREIRA, Rosa M. R.
    Objectives To describe the frequency and investigate potential associations of unemployment, need of financial assistance and health-related quality of life in adult patients with childhood-onset Systemic Lupus Erythematosus (cSLE). Methods In this multicenter cross-sectional retrospective cohort study including cSLE adult patients, questionnaires were applied evaluating demographic characteristics, medical history, treatment, receipt of government financial assistance, work status, quality of life, economic classification, disease activity, and damage accrual. Disease activity and disease damage were measured at the study visit. Results Sixty-nine cSLE patients with a median age of 21 years from two Brazilian tertiary centers were included (median disease duration 9 years). Twenty-eight (40.6%) patients were unemployed and 16 (23.2%) were receiving financial assistance or retirement pension. Work unemployment was associated with higher damage scores (OR 1.83, 95% CI 1.08 to 3.09, p = 0.024), and the need of financial assistance was associated with longer disease duration (OR 1.15, 95% CI 1.00 to 1.31, p = 0.045) and worse economic score (OR 0.87, 95% CI 0.77 to 0.99, p = 0.038). Emotional health and body image perception were the most compromised domains of quality of life but showed no association with disease parameters. Disease activity, on the other hand, was inversely associated with symptoms scores (beta = -1.377, p = 0.014) and scores of adverse effects of medications (beta = -1.286, p = 0.020). Conclusion cSLE is a disease with severe outcomes and high social burden that profoundly impacts patients. Damage accrual is a major contributor to unemployment during adulthood and its prevention must be central in the management of cSLE.
  • article 4 Citação(ões) na Scopus
    HR-pQCTin vivoimaging of periarticular bone changes in chronic inflammatory diseases: Data from acquisition to impact on treatment indications
    (2021) FIGUEIREDO, Camille P.; PEREZ, Mariana O.; SALES, Lucas Peixoto; SCHETT, Georg; PEREIRA, Rosa M. R.
    Imaging is essential for the assessment of bone and inflammatory joint diseases. There are several imaging techniques available that differ regarding resolution, radiation exposure, time expending, precision, cost, availability or ability to predict disease progression. High-resolution peripheral quantitative computed tomography (HR-pQCT) that was introduced in 2004 allows thein vivoevaluation of peripheral bone microarchitecture and demonstrated high precision in assessing bone changes in inflammatory musculoskeletal diseases. This review summarizes the use of HR-pQCT for the evaluation of the hand skeleton in inflammatory joint diseases. We conducted a review of the literature regarding the protocols that involve hand joints assessment and evaluation of bone changes as erosions and osteophytes in chronic inflammatory diseases. Apart from measuring bone density and structure of the radius and the tibia, HR-pQCT has contributed to assessment of bone erosions and osteophytes, considered the hallmark of diseases as rheumatoid arthritis and psoriatic arthritis, respectively. In this way, there are some conventions recently established by rheumatic study groups that we just summarized here in order to standardize HR-pQCT measurements.
  • conferenceObject
    Impaired Kidney Functional In Histidine Dipeptide Depleted Animals. An Exploratory Study With Carns1 Knockout Rats
    (2022) GONCALVES, Livia S.; NATALI, Jose; SHIMIZU, Maria Heloisa M.; SALES, Lucas P.; SAITO, Tiemi; FERNANDES, Alan L.; GUALANO, Bruno; SEGURO, Antonio Carlos; ARTIOLI, Guilherme G.
  • article 8 Citação(ões) na Scopus
    Insulin does not stimulate beta-alanine transport into human skeletal muscle
    (2020) GONCALVES, Livia de Souza; KRATZ, Caroline; SANTOS, Livia; CARVALHO, Victor Henrique; SALES, Lucas Peixoto; NEMEZIO, Kleiner; LONGOBARDI, Igor; RIANI, Luiz Augusto; LIMA, Marcelo Miranda de Oliveira; SAITO, Tiemi; FERNANDES, Alan Lins; RODRIGUES, Joice; JAMES, Ruth Margaret; SALE, Craig; GUALANO, Bruno; GELONEZE, Bruno; MEDEIROS, Marisa Helena Gennari de; ARTIOLI, Guilherme Giannini
    To test whether high circulating insulin concentrations influence the transport of beta-alanine into skeletal muscle at either saturating or subsaturating beta-alanine concentrations, we conducted two experiments whereby beta-alanine and insulin concentrations were controlled. In experiment 1, 12 men received supraphysiological amounts of beta-alanine intravenously (0.11 for 150 min), with or without insulin infusion. beta-Alanine and carnosine were measured in muscle before and 30 min after infusion. Blood samples were taken throughout the infusion protocol for plasma insulin and beta-alanine analyses. beta-Alanine content in 24-h urine was assessed. In experiment 2, six men ingested typical doses of beta-alanine (10 mg/kg) before insulin infusion or no infusion. beta-Alanine was assessed in muscle before and 120 min following ingestion. In experiment 1, no differences between conditions were shown for plasma beta-alanine, muscle beta-alanine, muscle carnosine and urinary beta-alanine concentrations (all P > 0.05). In experiment 2, no differences between conditions were shown for plasma beta-alanine or muscle beta-alanine concentrations (all P > 0.05). Hyperinsulinemia did not increase beta-alanine uptake by skeletal muscle cells, neither when substrate concentrations exceed the V-max of beta-alanine transporter TauT nor when it was below saturation. These results suggest that increasing insulin concentration is not necessary to maximize beta-alanine transport into muscle following beta-alanine intake.
  • conferenceObject
    (2023) FRANCO, A. Silva; MURAI, I.; YANG, T.; SALES, L. Peixoto; GUEDES, L.; PASOTO, S.; FIGUEIREDO, C.; PEREIRA, R. M.
  • article 2 Citação(ões) na Scopus
    Bone erosions associated with systemic bone loss on HR-pQCT in women with longstanding polyarticular juvenile idiopathic arthritis
    (2023) RIBEIRO, Surian Clarisse C. R.; SALES, Lucas P.; FERNANDES, Alan L.; PEREZ, Mariana O.; TAKAYAMA, Liliam; CAPARBO, Valeria F.; ASSAD, Ana Paula L.; AIWAKA, Nadia E.; GOLDENSTEIN-SCHAINBERG, Claudia; BORBA, Eduardo F.; DOMICIANO, Diogo S.; FIGUEIREDO, Camille P.; PEREIRA, Rosa M. R.
    Objectives: To analyze longstanding polyarticular juvenile idiopathic arthritis (pJIA) for possible associations between localized bone damage (erosions), and systemic bone loss. Besides, to compare the systemic bone mass of pJIA with healthy controls. Methods: Thirty-four pJIA women and 99 healthy controls (HC) were included. Radius and tibia of all subjects were scanned by HR-pQCT. Volumetric bone mineral density (vBMD), bone microarchitecture, and -finite element parameters were analyzed. Patients underwent HR-pQCT of 2nd and 3rd metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the dominant hand, for bone erosions quantification. Results: The mean age of patients was 31.5 +/- 7.4yrs with a mean disease duration of 21.7 +/- 9.2yrs. Bone erosions were detectable in 79% of patients. The number of bone erosions was positively correlated with cortical porosity (Ct.Po) at tibia (r = 0.575, p = 0.001), and radius (r = 0.423, p = 0.018); and negatively correlated with cortical vBMD at tibia (r=-0.420, p = 0.015). In a logistic regression analysis, adjusted for anti-CCP, the presence of bone erosions was independently associated with Ct.Po at radius (p = 0.018) and cortical vBMD at tibia (p = 0.020). Moreover, cortical and trabecular vBMD, trabecular number, and mu-finite element parameters were decreased in patients compared to HC (p < 0.05). Conclusion: Bone erosions in longstanding pJIA women were associated with decreased cortical bone parameters, and these patients showed systemic bone impairment at peripheral sites compared with healthy controls.
  • conferenceObject
    Bone Erosions and Osteophytes in Premenopausal Women with Long-standing Rheumatoid Arthritis: Association with Systemic Bone Involvement Using HR-pQCT
    (2021) PEREZ, Mariana; FIGUEIREDO, Camille; SALES, Lucas; MEDEIROS-RIBEIRO, Ana; TAKAYAMA, Liliam; DOMICIANO, Diogo; BONFIGLIOLI, Karina; CAPARBO, Valeria; PEREIRA, Rosa
  • article 12 Citação(ões) na Scopus
    Histidine dipeptides are key regulators of excitation-contraction coupling in cardiac muscle: Evidence from a novel CARNS1 knockout rat model
    (2021) GONCALVES, Livia de Souza; SALES, Lucas Peixoto; SAITO, Tiemi Raquel; CAMPOS, Juliane Cruz; FERNANDES, Alan Lins; NATALI, Jose; JENSEN, Leonardo; ARNOLD, Alexandre; RAMALHO, Lisley; BECHARA, Luiz Roberto Grassmann; ESTECA, Marcos Vinicius; CORREA, Isis; SANT'ANNA, Diogo; CERONI, Alexandre; MICHELINI, Lisete Compagno; GUALANO, Bruno; TEODORO, Walcy; CARVALHO, Victor Henrique; VARGAS, Bianca Scigliano; MEDEIROS, Marisa Helena Gennari; BAPTISTA, Igor Luchini; IRIGOYEN, Maria Claudia; SALE, Craig; FERREIRA, Julio Cesar Batista; ARTIOLI, Guilherme Giannini
    Histidine-containing dipeptides (HCDs) are abundantly expressed in striated muscles. Although important properties have been ascribed to HCDs, including H+ buffering, regulation of Ca2+ transients and protection against oxidative stress, it remains unknown whether they play relevant functions in vivo. To investigate the in vivo roles of HCDs, we developed the first carnosine synthase knockout (CARNS1-/-) rat strain to investigate the impact of an absence of HCDs on skeletal and cardiac muscle function. Male wild-type (WT) and knockout rats (4 months-old) were used. Skeletal muscle function was assessed by an exercise tolerance test, contractile function in situ and muscle buffering capacity in vitro. Cardiac function was assessed in vivo by echocardiography and cardiac electrical activity by electrocardiography. Cardiomyocyte contractile function was assessed in isolated cardiomyocytes by measuring sarcomere contractility, along with the determination of Ca2+ transient. Markers of oxidative stress, mitochondrial function and expression of proteins were also evaluated in cardiac muscle. Animals were supplemented with carnosine (1.8% in drinking water for 12 weeks) in an attempt to rescue tissue HCDs levels and function. CARNS1-/- resulted in the complete absence of carnosine and anserine, but it did not affect exercise capacity, skeletal muscle force production, fatigability or buffering capacity in vitro, indicating that these are not essential for pH regulation and function in skeletal muscle. In cardiac muscle, however, CARNS1-/- resulted in a significant impairment of contractile function, which was confirmed both in vivo and ex vivo in isolated sarcomeres. Impaired systolic and diastolic dysfunction were accompanied by reduced intracellular Ca2+ peaks and slowed Ca2+ removal, but not by increased markers of oxidative stress or impaired mitochondrial respiration. No relevant increases in muscle carnosine content were observed after carnosine supplementation. Results show that a primary function of HCDs in cardiac muscle is the regulation of Ca2+ handling and excitation-contraction coupling.
  • article 2 Citação(ões) na Scopus
    Lower hand grip in rheumatoid arthritis patients is associated with low finite element analysis using high resolution peripheral quantitative computed tomography scan of the 2nd metacarpophalangeal joint
    (2022) FIGUEIREDO, Camille Pinto; PEREZ, Mariana Ortega; SALES, Lucas Peixoto; DOMICIANO, Diogo Souza; SAMPAIO-BARROS, Marilia M.; CAPARBO, Valeria de Falco; PEREIRA, Rosa Maria Rodrigues
    Aim To evaluate hand function by hand grip test in rheumatoid arthritis (RA) patients, and its association with bone erosions and the estimated bone strength (finite element - FE analysis) through the analysis of the 2nd metacarpal head of the dominant hand using high resolution peripheral quantitative computed tomography (HR-pQCT). Method Eighty-two female RA patients between 18-50 years old were selected. Demographic data, Health Questionnaire Assessment Disability Index (HAQ), Disease Activity Score of 28 joints (DAS)-28, simplified disease activity index (SDAI) and the hand grip test were set. The HR-pQCT scans of 2nd metacarpophalangeal joints of the dominant hand of all patients were performed according to SPECTRA group protocols. The images were used to assess bone erosions and FE analysis. The hand grip test was categorized in 2 groups and separately compared (< 18 vs >= 18 kgf). A logistic regression was performed using hand grip test A significant difference was found between the 2 groups regarding HAQ, inflammatory markers (erythrocyte sedimentation rate, C-reactive protein), DAS-28, SDAI, total volume of erosion and bone strength parameter (FE analysis - Failure Load [F.Load]). The logistic regression analysis showed that the risk factors associated with hand grip test <18 kgf were higher SDAI (odds ratio [OR] 0.912; 95% CI 0.837-0.993) and lower values of bone strength parameter (F.Load) (OR 1.007; 95% CI 1.002-1.012). Conclusion Lower values of hand grip test were associated with higher disease activity score-SDAI and lower bone strength of 2nd metacarpal bone head of the dominant hand evaluated here through a FE analysis using HR-pQCT scan.
  • article 1 Citação(ões) na Scopus
    Transcriptomic characterization of classical monocytes highlights the involvement of immuno-inflammation in bone erosion in Rheumatoid Arthritis
    (2023) SALES, Lucas Peixoto; HOUNKPE, Bidossessi Wilfried; PEREZ, Mariana Ortega; CAPARBO, Valeria Falco; DOMICIANO, Diogo Souza; BORBA, Eduardo Ferreira; SCHETT, Georg; FIGUEIREDO, Camille Pinto; PEREIRA, Rosa Maria Rodrigues
    Introduction: Evidence-based data suggest that under inflammatory conditions, classical monocytes are the main source of osteoclasts and might be involved in bone erosion pathophysiology. Here, we analyze the transcriptomic profile of classical monocytes in erosive and non-erosive rheumatoid arthritis patients in order to better understand their contribution to bone erosion.Methods: Thirty-nine premenopausal RA patients were consecutively enrolled and divided into two groups based on the presence of bone erosions on hand joints. Classical monocytes were isolated from peripheral blood through negative selection, and RNA-seq was performed using a poly-A enrichment kit and Illumina (R) platform. Classical monocytes transcriptome from healthy age-matched women were also included to identify differentially expressed genes (DEGs). Therefore, gene sets analysis was performed to identify the enriched biological pathways.Results: RNA-seq analysis resulted in the identification of 1,140 DEGs of which 89 were up-regulated and 1,051 down-regulated in RA patients with bone erosion compared to those without bone erosions. Among up-regulated genes, there was a highlighted expression of IL18RAP and KLF14 related to the production of pro-inflammatory cytokines, innate and adaptive immune response. Genes related to collagen metabolism (LARP6) and bone formation process (PAPPA) were down-regulated in RA patients with erosions. Enriched pathways in patients with erosions were associated with greater activation of immune activation, and inflammation. Interestingly, pathways associated with osteoblast differentiation and regulation of Wnt signaling were less activated in RA patients with erosions.Conclusion: These findings suggest that alterations in expression of monocyte genes related to the inflammatory process and impairment of bone formation might have an important role in the pathophysiology of bone erosions in RA patients.