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Brazilian Journal of Medical and Biological Research, Volume: 52, Número: 8, Publicado: 2019
  • Ventilation distribution as a contributor to the functional exercise capacity in patients with systemic sclerosis-associated interstitial lung disease without pulmonary hypertension Research Article

    Andrade, F.M.; Oliveira, A.D.; Lopes, A.J.

    Resumo em Inglês:

    Phenotypic differences have been described between patients with systemic sclerosis (SSc)-associated interstitial lung disease (ILD) and SSc-associated pulmonary hypertension, including performance differences in the 6-min walk test (6MWT). Moreover, the correlations between the 6MWT and traditional pulmonary function tests (PFTs) are weak, indicating the need to search for new parameters that explain exercise performance. Thus, our objective was to evaluate the impact of ventilation distribution heterogeneity assessed by the nitrogen single-breath washout (N2SBW) test and peripheral muscle dysfunction on the exercise capacity in patients with SSc-ILD and limited involvement of the pulmonary parenchyma. In this cross-sectional study, 20 women with SSc-ILD and 20 matched controls underwent PFTs (including spirometry, diffusing capacity for carbon monoxide (DLco), and the N2SBW test) and performed the 6MWT and knee isometric dynamometry. The 6-min walking distance (6MWD, % predicted) was strongly correlated with the phase III slope of the single-breath nitrogen washout (phase III slopeN2SBW) (r=−0.753, P<0.0001) and reasonably correlated with the forced vital capacity (FVC) (r=0.466, P=0.008) and DLco (r=0.398, P=0.011). The peripheral oxygen saturation (SpO2) during exercise was not significantly correlated with any of the pulmonary or muscle function parameters. The phase III slopeN2SBW was the only predictive variable for the 6MWD, whereas quadriceps strength and FVC/DLco were predictive variables for SpO2. Ventilation distribution heterogeneity is one factor that contributes to a lower 6MWD in SSc-ILD patients. In addition, muscle dysfunction and abnormal lung diffusion at least partly explain the decreased SpO2 of these patients.
  • MicroRNA-383-5p inhibits the progression of gastric carcinoma via targeting HDAC9 expression Research Article

    Xu, Gang; Li, Na; Zhang, Yan; Zhang, Jinbiao; Xu, Rui; Wu, Yanling

    Resumo em Inglês:

    MicroRNAs (miRNAs), as post-transcriptional regulators, have been reported to be involved in the initiation and progression of various types of cancer, including gastric cancer (GC). The present study aimed to investigate the role of miR-383-5p in gastric carcinogenesis. Cell viability was analyzed using CCK-8 kit. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was used to evaluate cell apoptosis. The expression levels of miR-383-5p and histone deacetylase 9 (HDAC9) mRNA in GC tissues and cell lines were analyzed using RT-qPCR. The protein expression of HDAC9 was detected by western blotting. We found that HDAC9 was up-regulated and miR-383-5p was down-regulated in GC tissues and cell lines. High HDAC9 expression or low miR-383-5p expression was closely related to poor prognosis and metastasis in GC patients. HDAC9 knockout or miR-383-5p mimics led to growth inhibition and increased apoptosis in AGS and SGC-7901 cells. More importantly, we validated that miR-383-5p as a post-transcriptional regulator inhibited HDAC9 expression and was inversely correlated with HDAC9 expression in GC tissues. miR-383-5p had the opposite effects to HDAC9 in gastric carcinogenesis. miR-383-5p played an important role in gastric carcinogenesis, and it is one of the important mechanisms to regulate oncogenic HDAC9 in GC, which might be helpful in the development of novel therapeutic strategies for the treatment of GC.
  • Gene expression profiling reveals upregulated FUT1 and MYBPC1 in children with pancreaticobiliary maljunction Research Article

    Guo, Wan-Liang; Geng, Jia; Zhao, Jun-gang; Fang, Fang; Huang, Shun-Gen; Wang, Jian

    Resumo em Inglês:

    Pancreaticobiliary maljunction (PBM) is associated with high risk of epithelial atypical growth and malignant transformation of the bile duct or gallbladder. However, overall changes in genetic expression have not been examined in children with PBM. Genome-wide expression was analyzed using peripheral blood samples from 10 children with PBM and 15 pediatric controls. Differentially expressed genes (DEGs) were identified using microarray. Bioinformatics analysis was conducted using Gene Ontology and KEGG analyses. The top 5 in the up-regulated genes in PBM were verified with qRT-PCR. Receiver operator characteristic curve analysis was conducted to evaluate the predictive accuracy of selected genes for PBM. The microarray experiments identified a total of 876 DEGs in PBM, among which 530 were up-regulated and the remaining 346 were down-regulated. Verification of the top 5 up-regulated genes (TYMS, MYBPC1, FUT1, XAGE2, and GREB1L) by qRT-PCR confirmed the up-regulation of MYBPC1 and FUT1. Receiver operating characteristic curve analysis suggested that FUT1 and MYBPC1 up-regulation could be used to predict PBM, with the area under the curve of 0.873 (95%CI=0.735−1.000) and 0.960 (95%CI=0.891−1.000), respectively. FUT1 and MYBPC1 were up-regulated in children with PBM, and could be used as potential biomarkers for PBM.
  • Association between BDNF G196A (Val66Met) polymorphism and cognitive impairment in patients with Parkinson's disease: a meta-analysis Research Article

    Wang, Qian; Liu, Jianfang; Guo, Yikun; Dong, Guanzhong; Zou, Wenying; Chen, Zhuoyou

    Resumo em Inglês:

    Brain-derived neurotrophic factor (BDNF) is widely expressed in the central nervous system and prolongs the survival of dopaminergic neurons in the substantia nigra. Several studies have recently investigated the association between BDNF G196A (Val66Met), a single nucleotide polymorphism influencing cognitive processes, and cognitive impairment in Parkinson's disease (PD), but with contradictory findings. Thus, this meta-analysis was performed to clarify the possible association. Relevant studies were identified by a systematic search of PubMed, Embase, and China National Knowledge Infrastructure (CNKI) databases. The strength of the association was evaluated using crude odds ratios and 95% confidence interval. Finally, six studies involving 532 cases and 802 controls were included. Our analyses suggested the G196A (Val66Met) polymorphism was significantly associated with cognitive impairment in PD, especially in Caucasian populations. In conclusion, BDNF G196A (Val66Met) is confirmed to be a risk factor for cognitive impairment in PD.
  • Presence of age- and sex-related differences in heart rate variability despite the maintenance of a suitable level of accelerometer-based physical activity Research Article

    Spina, G.D.; Gonze, B.B.; Barbosa, A.C.B.; Sperandio, E.F.; Dourado, V.Z.

    Resumo em Inglês:

    There is currently a lack of information adjacent on the influence of sex and age in heart rate variability (HRV), adjusted according to accelerometer-based physical activity (PADL). We hypothesized that the effect of sex and age on the HRV should be reduced or absent in individuals with a suitable PADL level. We aim to evaluate the influence of sex and age on HRV, adjusted for the confounding effects of the PADL level. A total of 485 age-stratified subjects (18–39, 40–59, and ≥60 years) underwent HRV analyses at rest and 7-day assessments of accelerometer-based PADL. Multivariate analyses of covariance were done using log-transformed HRV indices as outcomes, age and sex as fixed factors, and PADL, cardiovascular risk, fat body mass, and heart rate (HR) at rest as covariates. Despite the adjustment for directly measured PADL, women had better indices of vagal tone, whereas men had higher sympathetic influence. Also, compared to middle-aged and older adults, younger individuals (ages 18–39 years) presented better HRV. Multiple regression analyses confirmed that age and sex were the main predictors of HRV indices, even after adjusting for PADL directly assessed by triaxial accelerometer and HR. We also observed that the correlation between some HRV indexes and the different indexes of physical activity directly evaluated was significant, but not very consistent. Thus, HRV indices are influenced by age and sex, regardless of accelerometer-based physical activity. Interventions with physical activity and exercise aimed at improving the autonomic modulation of asymptomatic adults should take such differences into account.
  • Recurrent hepatitis C treatment with direct acting antivirals – a real life study at a Brazilian liver transplant center Research Article

    Zanaga, L.P.; Santos, A.G.; Ataíde, E.C.; Boin, I.F.S.F.; Stucchi, R.S.B.

    Resumo em Inglês:

    Recurrent hepatitis C (HCV) after liver transplantation (LT) is an important cause of morbidity and mortality. Antiviral treatment is recommended to avoid unfavorable outcomes. Direct-acting antivirals (DAA) have transformed HCV treatment, with higher efficacy and fewer side-effects than interferon-based therapies traditionally used. To evaluate DAA treatment outcomes at a Brazilian transplant unit, data of patients who finished HCV treatment at the Liver Transplant Unit of the University of Campinas were analyzed. Treatment consisted of sofosbuvir, daclatasvir, and ribavirin, for 12 or 24 weeks, according to the national guidelines. Fifty-five patients completed antiviral treatment and 54 had HCV-viral load results available. The majority of patients were male (78%), 58 years old on average, 65% had hepatocellular carcinoma (HCC) before LT, and 67% were interferon treatment-experienced. Most patients had HCV genotype 1 (65%), 35% had genotype 3, and started treatment on an average of 38 months after LT (range: 2–228). Fifty-eight percent were treated for 12 weeks and 42% for 24 weeks, using a mean dose of ribavirin of 10.1 mg/kg (4.2–16.1). There were no treatment interruptions due to serious side effects. The sustained virological response rate was 98%. Only one patient relapsed, a genotype 3 cirrhotic treated for 12 weeks. The average follow-up after starting antivirals was 20 months. There were no recurrences of HCC, but there was one rejection episode and one cirrhosis decompensation episode, both 12 weeks after treatment. DAA treatment is safe and effective in the post-LT setting and was not associated to HCC recurrence in the cohort studied.
  • Comparison of three PET methods to assess peritoneal membrane transport Research Article

    Romani, RF.; Waniewski, J.; Kruger, L.; Lindholm, B.; Nascimento, M.M.

    Resumo em Inglês:

    The peritoneal equilibration test (PET) is the most widespread method for assessing water and solute transport across the peritoneal membrane. This study compared three methods: traditional PET (t-PET), mini-PET, and modified PET (mod-PET). Non-diabetic adults (n=21) who had been on peritoneal dialysis (PD) for at least three months underwent t-PET (glucose 2.5%-4 h), mini-PET (glucose 3.86%-1 h), and mod-PET (glucose 3.86%-4 h) to determine dialysate-to-plasma concentration ratio (D/P) for creatinine and dialysate-to-baseline dialysate concentration ratio (D/D0) for glucose. Agreement between methods regarding D/P creatinine and D/D0 glucose was assessed using analysis of variance (ANOVA), Pearson's correlation coefficient, and Bland-Altman analysis. D/P creatinine differed between t-PET and mini-PET (P<0.001) and between mod-PET and mini-PET (P<0.01) but not between t-PET and mod-PET (P=0.746). The correlation of D/P creatinine with t-PET vs mod-PET was significant (r=0.387, P=0.009) but not that of t-PET vs mini-PET (r=0.088, P=0.241). Estimated bias was −0.029 (P=0.201) between t-PET and mod-PET, and 0.206 (P<0.001) between t-PET and mini-PET. D/D0 glucose differed between t-PET and mod-PET (P=0.003) and between mod-PET and mini-PET (P=0.002) but not between t-PET and mini-PET (P=0.885). The correlations of D/D0 glucose in t-PET vs mod-PET (r=−0.017, P=0.421) or t-PET vs mini-PET (r=0.152, P=0.609) were not significant. Estimated bias was 0.122 (P=0.026) between t-PET and mod-PET, and 0.122 (P=0.026) between t-PET and mini-PET. The significant correlation of D/P creatinine between t-PET and mod-PET suggested that the latter is a good alternative to t-PET. There was no such correlation between t-PET and mini-PET.
  • Decreased respiratory performance of children and adolescents with myelomeningocele who use a wheelchair – preliminary data Research Article

    Martins, E.J.; Gastaldi, A.C.; Davoli, G.B.Q.; Leonardi-Figueiredo, M.M.; Mattiello-Sverzut, A.C.

    Resumo em Inglês:

    Myelomeningocele (MMC) is a neural tube defect that often causes spinal cord injury at the thoracolumbar region, as well as sensory and motor paralysis in the lower limbs. This leads to continuous use of a wheelchair and, consequently, a sedentary lifestyle, predisposition to muscle weakness, cardiovascular and respiratory disorders, obesity, and structural alterations in the spine. We assessed the respiratory function and shoulder strength of MMC participants who were wheelchair-users and had no respiratory complaints and compared them to healthy children and adolescents. MMC (n=10) and healthy (n=25) participants of both genders with a mean age of 12.45 years (SD=2.1) were assessed for weight, height, respiratory performance, and isometric peak for shoulder flexors, extensors, abductors, and adductors, using an isokinetic dynamometer. Medullary lesion, functional levels, and abnormal curvatures of the spine were assessed for MMC participants. The level of spinal cord injury for the majority of the MMC participants was high lumbar and they had scoliosis. MMC showed lower values for forced vital capacity, forced expiratory volume at the first second, forced expiratory flow (25–75%), maximal voluntary ventilation, and isometric peak for shoulder flexors and adductors compared to healthy participants. This indicated a decreased vital capacity, respiratory muscle endurance, and shoulder muscle strength.
  • Does whole body vibration exercise improve oxidative stress markers in women with fibromyalgia? Research Article

    Santos, J.M.; Mendonça, V.A.; Ribeiro, V.G.C.; Tossige-Gomes, R.; Fonseca, S.F.; Prates, A.C.N.; Flor, J.; Oliveira, A.C.C.; Martins, J.B.; Garcia, B.C.C.; Leite, H.R.; Figueiredo, P.H.S.; Bernardo-Filho, M.; Lacerda, A.C.R.

    Resumo em Inglês:

    The objective of this study was to investigate the effect of whole body vibration (WBV) exercise on oxidative stress markers in a group of women with fibromyalgia (FM) compared to a group of healthy women (CT). Twenty-one women diagnosed with FM and 21 age- and weight-matched healthy women were enrolled the study. Plasma oxidative stress markers (primary outcomes) were evaluated at rest and after WBV, and included thiobarbituric acid reactive substances (TBARS), iron reduction capacity (FRAP), superoxide dismutase antioxidant enzymes activity (SOD), and catalase (CAT). At rest, the FM group had higher TBARS (P<0.001) and FRAP (P<0.001), and lower CAT (P=0.005) compared to the CT. In the CT group, the WBV had no effect on TBARS (P=0.559) and FRAP (P=0.926), whereas it increased both SOD (P<0.001) and CAT (P<0.001). In the FM group, the WBV reduced TBARS (p <0.001), FRAP (P<0.001), and CAT (P=0.005), while it increased SOD (P=0.019). There was an interaction effect (moments vs groups) in the TBARS (effect size=1.34), FRAP (effect size=0.93), CAT (effect size=1.45), and SOD (effect size=1.44) (P<0.001). A single trial of WBV exercise improved all oxidant and antioxidant parameters towards a greater adaptation to the stress response in FM women.
  • Reproducibility of carotid ultrasound measurements in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) at baseline Research Article

    Santos-Neto, P.J.; Sena-Santos, E.H.; Meireles, D.P.; Santos, I.S.; Bensenor, I.M.; Lotufo, P.A.

    Resumo em Inglês:

    Carotid artery assessment by ultrasound is a non-invasive evaluation of subclinical atherosclerosis and a predictor of cardiovascular events. However, ultrasound examinations are operator-dependent. In the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), ultrasound images have been acquired from more than 10,000 participants. In this article, we describe the reproducibility of carotid intima-media thickness (CIMT), carotid plaque detection, and carotid plaque score (defined as the number of arterial sites with plaques) using ELSA-Brasil protocol, in a subset of 118 participants. Two board-certified radiologists and a trained technician read carotid images. We calculated intra- and inter-observer intraclass correlation (ICC) for CIMT values. We also present kappa coefficients for plaque detection and weighted kappa coefficients for carotid plaque score. Participants were aged 58.2±6.6 years, and 60 (50.8%) were men. For common carotid artery CIMT measurements, intra- and inter-observer ICC values were very good to excellent, ranging from 0.90 (95% confidence interval [95%CI]: 0.72–0.95) to 0.98 (95%CI: 0.97–0.99). For carotid plaque, intra- (0.96 [95%CI: 0.96–0.96]) and inter- (0.99 [95%CI: 0.99–0.99]) observer weighted kappa coefficients were very good. Intra- and inter-observer Kappa coefficients for the presence of plaques by site were good to very good, ranging from 0.69 to 1.00. In conclusion, we found very good reproducibility for carotid plaque score and CIMT measurements in the ELSA-Brasil at baseline. These results are comparable to the best findings from similar large cohorts that analyzed carotid ultrasound data.
  • Poly(trimethylene carbonate-co-L-lactide) electrospun scaffolds for use as vascular grafts Research Article

    Braghirolli, D.I.; Caberlon, B.; Gamba, D.; Petry, JFTC.; Dias, M.L.; Pranke, P.

    Resumo em Inglês:

    Currently, there is great clinical need for suitable synthetic grafts that can be used in vascular diseases. Synthetic grafts have been successfully used in medium and large arteries, however, their use in small diameter vessels is limited and presents a high failure rate. In this context, the aim of this study was to develop tissue engineering scaffolds, using poly(trimethylene carbonate-co-L-lactide) (PTMCLLA), for application as small diameter vascular grafts. For this, copolymers with varying trimethylene carbonate/lactide ratios – 20/80, 30/70, and 40/60 – were submitted to electrospinning and the resulting scaffolds were evaluated in terms of their physicochemical and biological properties. The scaffolds produced with PTMCLLA 20/80, 30/70, and 40/60 showed smooth fibers with an average diameter of 771±273, 606±242, and 697±232 nm, respectively. When the degradation ratio was evaluated, the three scaffold groups had a similar molecular weight (Mw) on the final day of analysis. PTMCLLA 30/70 and 40/60 scaffolds exhibited greater flexibility than the PTMCLLA 20/80. However, the PTMCLLA 40/60 scaffolds showed a large wrinkling and their biological properties were not evaluated. The PTMCLLA 30/70 scaffolds supported the adhesion and growth of mesenchymal stem cells (MSCs), endothelial progenitor cells, and smooth muscle cells (SMCs). In addition, they provided a spreading of MSCs and SMCs. Given the results, the electrospun scaffolds produced with PTMCLLA 30/70 copolymer can be considered promising candidates for future applications in vascular tissue engineering.
  • Diagnostic value of circulating lncRNA ANRIL and its correlation with coronary artery disease parameters Research Article

    Hu, Yao; Hu, Jing

    Resumo em Inglês:

    This study aimed to detect the expression of the long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) and evaluate its correlation with disease risk, stenosis degree, inflammation, as well as overall survival (OS) in coronary artery disease (CAD) patients. A total of 230 patients who underwent diagnostic coronary angiography were consecutively recruited and assigned to CAD group (n=125) or control group (n=105) according to presence or absence of CAD. Gensini score was calculated to assess the severity of coronary artery damage. Plasma samples were collected and the expression ANRIL was detected in all participants. High-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), and cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, IL-8, IL-10, and IL-17 in CAD patients were measured and OS was calculated. The relative expression of ANRIL was higher in CAD patients compared to controls (P<0.001). Receiver operating characteristic disclosed that ANRIL could distinguish CAD patients from controls with an area under the curve of 0.789 (95%CI: 0.731–0.847). Spearman's rank correlation test revealed that expression of ANRIL was positively correlated with Gensini score (P=0.001), levels of hs-CRP (P=0.001), ESR (P=0.038), TNF-α (P=0.004), and IL-6 (P<0.001), while negatively correlated with IL-10 level (P=0.008) in CAD patients. Kaplan-Meier curve revealed that high expression of ANRIL was associated with shorter OS (P=0.013). In conclusion, circulating ANRIL presented a good diagnostic value for CAD, and its high expression was associated with increased stenosis degree, raised inflammation, and poor OS in CAD patients.
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