Scielo RSS <![CDATA[Brazilian Journal of Medical and Biological Research]]> http://www.scielo.br/rss.php?pid=0100-879X20190007&lang=en vol. 52 num. 7 lang. en <![CDATA[SciELO Logo]]> http://www.scielo.br/img/en/fbpelogp.gif http://www.scielo.br <![CDATA[Henoch-Schönlein purpura nephritis associated with monoclonal gammopathy of renal significance: a case report]]> http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2019000700501&lng=en&nrm=iso&tlng=en Monoclonal gammopathy of renal significance (MGRS) can present with different morphologic features and lead to kidney failure. The Henoch-Schönlein purpura nephritis (HSPN) that cannot be relieved by treatment with glucocorticoid and immunosuppressive agents suggests the presence of monoclonal gammopathy in adult patients. The present study reports on a single case of HSPN associated with IgA-κMGRS. The patient who suffered from recurrent skin purpura for 6 months and nephrotic syndrome for 2 months was admitted to our hospital. Bone marrow biopsy showed monoclonal gammopathy of undetermined significance. Kidney biopsy indicated a Henoch-Schönlein purpura nephritis (HSPN, ISKDC classified as type III) with positive staining with κ-light chain in the glomeruli and renal tubular epithelial cells. Furthermore, skin biopsy showed leukocytoclastic vasculitis and negative staining for Congo red and light chain. Given both the renal and cutaneous involvement, the patient was considered to have HSPN associated with IgA-κMGRS. The patient experienced an exacerbation in his purpura-like lesions and clinical status after treatment with glucocorticoid and immunosuppressive agents. Consequently, the patient was put on a regimen that included dexamethasone (20 mg on the 1st, 4th, 8th, and 11th days of each month, iv) and bortezomib (2.4 mg on the 1st, 4th, 8th, and 11th days of each month, iv). Eight weeks after treatment, he had complete resolution of his cutaneous purpura and his biochemical parameters improved. The latent presence of MGRS in cases of HSPN should be considered in adult patients. Increased cognizance and correct treatment options could improve patient outcomes. <![CDATA[T cell receptor excision circles as a tool for evaluating thymic function in young children]]> http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2019000700601&lng=en&nrm=iso&tlng=en The thymus is a primary lymphoid organ responsible for the maturation of T cells as well as the immunological central tolerance. It is in the antenatal period and infancy that it plays its major role. In clinical practice, T cell receptor excision circles (TRECs) are considered a direct and reliable measure of the thymic function. TRECs are a by-product of DNA formation in gene rearrangement of T cell receptors. They are stable and they do not duplicate during mitosis, representing the recent emigrant T cells from the thymus. Despite their importance, TRECs have been neglected by physicians and there is a lack of data regarding thymic function during infancy of healthy children. In order to evaluate thymic function in the first years of life, we propose measuring TRECs as a valuable tool. One hundred and three blood samples from children and adolescents between 3 months and 20 years of age were analyzed. The mean TRECs count was 136.77±96.7 copies of TRECs/μL of DNA. The individuals between 0 and 5 years of age had significantly higher TRECs values than those between 10 and 20 years of age. No significant difference was observed in TRECs values among age groups below 5 years of age. An inverse correlation between TRECs and age was found (r=0.3 P=0.003). These data highlight and validate the evidence of decreased thymus function with age, even during infancy. Awareness should be raised with this important albeit ignored organ. <![CDATA[Baicalin ameliorates chronic mild stress-induced depression-like behaviors in mice and attenuates inflammatory cytokines and oxidative stress]]> http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2019000700602&lng=en&nrm=iso&tlng=en The natural flavonoid glycoside baicalin (BA) produces a variety of pharmaceutical effects, particularly for psychiatric/neurological disorders. This study evaluated the behavioral and neuroprotective effects of BA in mice subjected to chronic unpredictable mild stress, a model of depression. BA (25 and 50 mg/kg) significantly increased sucrose consumption and reduced immobility times in the tail suspension and forced swim tests, demonstrating that BA alleviated depression-like behaviors. Moreover, BA reduced the levels of inflammatory cytokines, such as interleukin 1β, interleukin 6, and tumor necrosis factor α, in serum and in the hippocampus. BA also abrogated increases in NMDAR/NR2B and Ca2+/calmodulin-dependent protein kinase II, and the decrease in phosphorylated ERK and reactive oxygen species production in mice subjected to chronic unpredictable mild stress. These findings suggested that the antidepressive effects of BA are due to the regulation of an NMDAR/NR2B-ERK1/2-related pathway and inhibition of inflammatory cytokines and oxidative stress. Thus, BA represents a potential candidate drug for patients suffering from depression. <![CDATA[Circulating high mobility group box-1 and toll-like receptor 4 expressions increase the risk and severity of epilepsy]]> http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2019000700603&lng=en&nrm=iso&tlng=en This study aimed to investigate the association of serum high-mobility group box-1 (HMGB1) and toll-like receptor 4 (TLR4) expressions with the risk of epilepsy as well as their correlations with disease severity and resistance to anti-epilepsy drugs. One hundred and five epilepsy patients and 100 healthy controls (HCs) were enrolled in this case-control study, and serum samples were collected from all participants to assess the HMGB1 and TLR4 expressions by enzyme-linked immunosorbent assay (ELISA). Both serum HMGB1 (P&lt;0.001) and TLR4 (P&lt;0.001) expressions were higher in epilepsy patients than in HCs, and they displayed good predictive values for risk of epilepsy. Moreover, HMGB1 was positively correlated with TLR4 level (r=0.735, P&lt;0.001). HMGB1 and TLR4 levels were both elevated in patients with an average seizure duration &gt;5 min compared to patients with a seizure duration ≤5 min (P=0.001 and P=0.014, respectively). Also, HMGB1 and TLR4 were increased in patients with seizure frequency &gt;3 times per month compared to patients with seizure frequency ≤3 times per month (both P=0.001). In addition, HMGB1 and TLR4 expressions were higher in intractable cases compared to drug-responsive cases (P&lt;0.001). In conclusion, both HMGB1 and TLR4 expressions were correlated with increased risk and severity of epilepsy and their level was higher in patients resistant to anti-epilepsy drugs. <![CDATA[FSH receptor binding inhibitor up-regulates ARID1A and PTEN genes associated with ovarian cancers in mice]]> http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2019000700604&lng=en&nrm=iso&tlng=en Experiments were conducted to determine if the follicle-stimulating hormone (FSH) receptor binding inhibitor (FRBI) impacts the expression levels of AT-rich interactive domain-containing protein 1A (ARID1A) and phosphatase and tensin homolog (PTEN) in ovaries and blood, as well as expressions of follicle-stimulating hormone cognate receptor (FSHR) gene and proteins. Mice in FRBI-10, FRBI-20, FRBI-30, and FRBI-40 groups were intramuscularly injected with 10, 20, 30, and 40 mg FRBI/kg, respectively, for five consecutive days. Western blotting and qRT-PCR were utilized to determine expression levels of ARID1A and PTEN proteins and mRNAs. Serum ARID1A and PTEN concentrations of the FRBI-40 group were higher than the control group (CG) and FSH group (P&lt;0.05). FSHR mRNA levels of FRBI-20, FRBI-30, and FRBI-40 groups were lower than that of CG and FSH groups on day 15 (P&lt;0.05 or P&lt;0.01). Expression levels of FSHR proteins of FRBI-30 and FRBI-40 groups were lower than those of CG and FSH groups (P&lt;0.05). Levels of ARID1A and PTEN proteins of the FRBI-30 group were greater than CG on days 20 and 30 (P&lt;0.05). FRBI doses had significant positive correlations to levels of ARID1A and PTEN proteins. Additionally, ARID1A and PTEN had negative correlations to FSHR mRNAs and proteins. A high dose of FRBI could promote the expression levels of ARID1A and PTEN proteins in ovarian tissues. FRBI increased serum concentrations of ARID1A and PTEN. However, FRBI depressed expression levels of FSHR mRNAs and proteins in mouse ovaries. <![CDATA[Epigallocatechin-3-gallate ameliorates lipopolysaccharide-induced acute lung injury by suppression of TLR4/NF-κB signaling activation]]> http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2019000700605&lng=en&nrm=iso&tlng=en Acute lung injury (ALI) is a serious clinical syndrome with a high rate of mortality. The activation of inflammation is well-recognized as a vital factor in the pathogenesis of lipopolysaccharide (LPS)-induced ALI. Therefore, suppression of the inflammatory response could be an ideal strategy to prevent ALI. Epigallocatechin-3-gallate (EGCG), mainly from green tea, has been shown to have an anti-inflammatory effect. The aim of the study was to explore whether EGCG alleviates inflammation in sepsis-related ALI. Male BALB/C mice were treated with EGCG (10 mg/kg) intraperitoneally (ip) 1 h before LPS injection (10 mg/kg, ip). The results showed that EGCG attenuated LPS-induced ALI as it decreased the changes in blood gases and reduced the histological lesions, wet-to-dry weight ratios, and myeloperoxidase (MPO) activity. In addition, EGCG significantly decreased the expression of pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in the lung, serum, and bronchoalveolar lavage fluid, and alleviated the expression of TLR-4, MyD88, TRIF, and p-p65 in the lung tissue. In addition, it increased the expression of IκB-α and had no influence on the expression of p65. Collectively, these results demonstrated the protective effects of EGCG against LPS-induced ALI in mice through its anti-inflammatory effect that may be attributed to the suppression of the activation of TLR 4-dependent NF-κB signaling pathways. <![CDATA[Reinforcement omission effects in rats with bilateral lesions in the substantia nigra pars compacta and ventral tegmental area]]> http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2019000700606&lng=en&nrm=iso&tlng=en Reinforcement omission effects (ROEs) are characterized by higher response rates after reinforcement omission than after reinforcement delivery. This pattern of behavior is interpreted in terms of motivational and attentional processes. Recent studies from our laboratory have shown that the amygdala, nucleus accumbens, and medial prefrontal cortex are involved in ROE modulation. Also, the literature has demonstrated a role of other areas such as substantia nigra pars compacta (SNc) and the ventral tegmental area (VTA) in processes related to surprising events, such as prediction error and presentation or omission of an event (exteroceptive stimulus and reinforcement). Since these structures send projections to areas related to ROE modulation such as the amygdala, nucleus accumbens, and prefrontal cortex, the objective of the present study was to determine whether the SNc and VTA also integrate the circuit involved in ROE modulation. Rats were trained on a fixed-interval 12 s with limited-hold 6 s signaled schedule of reinforcement (Pre-lesion training). After acquisition of stable performance, the rats received bilateral neurotoxic lesions of the SNc (Experiment 1) and VTA (Experiment 2). Following postoperative recovery, the rats were submitted to two refresher sessions (Post-lesion training). Subsequently, the training was changed from a 100 to a 50% schedule of reinforcement (Post-lesion testing). In both experiments, the results showed that there was no difference in performance between sham rats and rats with bilateral lesions of the SNc or the VTA. <![CDATA[Analysis of different levels of positive end-expiratory pressure during lung retrieval for transplantation: an experimental study]]> http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2019000700607&lng=en&nrm=iso&tlng=en Atelectasis and inadequate oxygenation in lung donors is a common problem during the retrieval of these organs. Nevertheless, the use of high positive end-expiratory pressure (PEEP) is not habitual during procedures of lung retrieval. Twenty-one Sprague-Dawley male consanguineous rats were used in the study. The animals were divided into 3 groups according to the level of PEEP used: low (2 cmH2O), moderate (5 cmH2O), and high (10 cmH2O). Animals were ventilated with a tidal volume of 6 mL/kg. Before lung removal, the lungs were inspected for the presence of atelectasis. When atelectasis was detected, alveolar recruitment maneuvers were performed. Blood gasometric analysis was performed immediately. Finally, the lungs were retrieved, weighed, and submitted to histological analysis. The animals submitted to higher PEEP showed higher levels of oxygenation with the same tidal volumes PO2=262.14 (PEEP 2), 382.4 (PEEP 5), and 477.0 (PEEP 10). The occurrence of atelectasis was rare in animals with a PEEP of 10 cmH2O, which therefore required less frequent recruitment maneuvers (need for recruitment: PEEP 2=100%, PEEP 5 =100%, and PEEP 10=14.3%). There was no change in hemodynamic stability, occurrence of pulmonary edema, or other histological injuries with the use of high PEEP. The use of high PEEP (10 cmH2O) was feasible and probably a beneficial strategy for the prevention of atelectasis and the optimization of oxygenation during lung retrieval. Clinical studies should be performed to confirm this hypothesis. <![CDATA[Age-related changes and effects of regular low-intensity exercise on gait, balance, and oxidative biomarkers in the spinal cord of Wistar rats]]> http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2019000700608&lng=en&nrm=iso&tlng=en The present study aimed to analyze age-related changes to motor coordination, balance, spinal cord oxidative biomarkers in 3-, 6-, 18-, 24-, and 30-month-old rats. The effects of low-intensity exercise on these parameters were also analyzed in 6-, 18-, and 24-month-old rats. Body weight, blood glucose, total cholesterol, and high-density lipoprotein (HDL) cholesterol were assessed for all rats. The soleus muscle weight/body weight ratio was used to estimate skeletal muscle mass loss. Body weight increased until 24 months; only 30-month-old rats exhibited decreased blood glucose and increased total cholesterol and HDL cholesterol. The soleus muscle weight/body weight ratio increased until 18 months, followed by a small decrease in old rats. Exercise did not change any of these parameters. Stride length and step length increased from adult to middle age, but decreased at old age. Stride width increased while the sciatic functional index decreased in old rats. Performance in the balance beam test declined with age. While gait did not change, balance improved after exercise. Aging increased superoxide anion generation, hydrogen peroxide levels, total antioxidant capacity, and superoxide dismutase activity while total thiol decreased and lipid hydroperoxides did not change. Exercise did not significantly change this scenario. Thus, aging increased oxidative stress in the spinal cord, which may be associated with age-induced changes in gait and balance. Regular low-intensity exercise is a good alternative for improving age-induced changes in balance, while beneficial effects on gait and spinal cord oxidative biomarkers cannot be ruled out because of the small number of rats investigated (n=5 or 6/group). <![CDATA[Ca<sup>2+/</sup>Calmodulin-dependent kinase II delta B is essential for cardiomyocyte hypertrophy and complement gene expression after LPS and HSP60 stimulation <em>in vitro</em>]]> http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2019000700609&lng=en&nrm=iso&tlng=en Inflammation plays an important role in the development of cardiovascular diseases (CVDs), suggesting that the immune system is a target of therapeutic interventions used for treating CVDs. This study evaluated mechanisms underlying inflammatory response and cardiomyocyte hypertrophy associated with bacterial lipopolysaccharide (LPS)- or heat shock protein 60 (HSP60)-induced Toll-like receptor (TLR) stimulation and the effect of a small interfering RNA (siRNA) against Ca2+/calmodulin-dependent kinase II delta B (CaMKIIδB) on these outcomes. Our results showed that treatment with HSP60 or LPS (TLR agonists) induced cardiomyocyte hypertrophy and complement system C3 and factor B gene expression. In vitro silencing of CaMKIIδB prevented complement gene transcription and cardiomyocyte hypertrophy associated with TLR 2/4 activation but did not prevent the increase in interleukin-6 and tumor necrosis factor-alfa gene expression in primary cultured cardiomyocytes. Moreover, CaMKIIδB silencing attenuated nuclear factor-kappa B expression. These findings supported the hypothesis that CaMKIIδB acts as a link between inflammation and cardiac hypertrophy. Furthermore, the present study is the first to show that extracellular HSP60 activated complement gene expression through CaMKIIδB. Our results indicated that a stress stimulus induced by LPS or HSP60 treatment promoted cardiomyocyte hypertrophy and initiated an inflammatory response through the complement system. However, CaMKIIδB silencing prevented the cardiomyocyte hypertrophy independent of inflammatory response induced by LPS or HSP60 treatment. <![CDATA[Association between elevated adiponectin level and adverse outcomes in patients with heart failure: a systematic review and meta-analysis]]> http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2019000700610&lng=en&nrm=iso&tlng=en Studies regarding the prognostic value of circulating adiponectin level in patients with heart failure are conflicting. The aim of this meta-analysis was to evaluate the association between elevated circulating adiponectin level and adverse outcomes in patients with heart failure. We searched PubMed and Embase databases from their inception to June 2018. Original observational studies that investigated the prognostic value of adiponectin in heart failure patients and reported all-cause mortality or combined endpoints of death/readmission as outcome measure were included. Pooled risk ratio (RR) with 95% confidence intervals (CI) were estimated by higher versus lower circulating adiponectin level. A total of 7 studies involving 862 heart failure patients were identified. Meta-analysis showed that heart failure patients with higher adiponectin level had significantly increased risk of all-cause mortality (RR 2.05; 95%CI 1.22–3.43) after adjustment for potential confounders. In addition, higher adiponectin level was associated with an increased risk of the combined endpoints of death/readmission (RR 2.22; 95%CI 1.38–3.57). Elevated baseline circulating adiponectin level is possibly associated with an increased risk of all-cause mortality and the combined endpoints of death/readmission in patients with heart failure. Determination of circulating adiponectin level has potential to improve risk stratification in heart failure patients. <![CDATA[Carotid intima-media thickness and plaques in internal carotid artery as surrogate markers of lower limb arterial lesions in Chinese patients with diabetic foot]]> http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2019000700611&lng=en&nrm=iso&tlng=en Peripheral arterial disease (PAD) can impair healing of diabetic foot (DF) in patients with diabetes mellitus. To determine whether carotid intima-media thickness (CIMT) can predict lower limb arterial lesions in patients with DF, this cross-sectional study enrolled patients with DF at West China Hospital (China) between January 2012 and December 2015. Ultrasonography was used to measure CIMT, assess the internal carotid arteries (ICA) for plaques, and evaluate lower limb segmental arteries for stenosis. The optimal CIMT cutoff for detecting lower limb PAD was determined by receiver operating characteristic (ROC) curve analysis. Factors associated with PAD were identified by logistic regression analyses. A total of 167 patients (mean age: 69.7±10.3 years; 102 men) were included. Patients with PAD were older and had higher levels of total cholesterol and low-density lipoprotein than patients without PAD (P&lt;0.05). The area under the ROC curve was 0.747 (P&lt;0.001). At the optimal CIMT cutoff of 0.71 mm, the sensitivity, specificity, positive predictive value, and negative predictive value were 79.65, 61.11, 81.08, and 58.93%, respectively. Compared with those without PAD, more patients with PAD had CIMT ≥0.71 mm (79.65 vs 38.89%; P&lt;0.001) and ICA plaques (66.37vs 11.11%; P&lt;0.001). Multivariate logistic regression revealed that age (odds ratio [OR]: 1.118; 95% confidence interval [95%CI]: 1.056–1.183; P&lt;0.001), ICA plaques (OR: 13.452; 95%CI: 4.450–40.662; P&lt;0.001), and CIMT ≥0.71 mm (OR: 2.802; 95%CI: 1.092–7.188; P=0.032) were associated with PAD.CIMT may be a surrogate marker of PAD in patients with DF. <![CDATA[Erratum for: “Effect of JJYMD-C, a novel synthetic derivative of gallic acid, on proliferation and phenotype maintenance in rabbit articular chondrocytes <em>in vitro</em>” [Braz J Med Biol Res (2014) 47(8): e3935]]]> http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2019000700901&lng=en&nrm=iso&tlng=en Peripheral arterial disease (PAD) can impair healing of diabetic foot (DF) in patients with diabetes mellitus. To determine whether carotid intima-media thickness (CIMT) can predict lower limb arterial lesions in patients with DF, this cross-sectional study enrolled patients with DF at West China Hospital (China) between January 2012 and December 2015. Ultrasonography was used to measure CIMT, assess the internal carotid arteries (ICA) for plaques, and evaluate lower limb segmental arteries for stenosis. The optimal CIMT cutoff for detecting lower limb PAD was determined by receiver operating characteristic (ROC) curve analysis. Factors associated with PAD were identified by logistic regression analyses. A total of 167 patients (mean age: 69.7±10.3 years; 102 men) were included. Patients with PAD were older and had higher levels of total cholesterol and low-density lipoprotein than patients without PAD (P&lt;0.05). The area under the ROC curve was 0.747 (P&lt;0.001). At the optimal CIMT cutoff of 0.71 mm, the sensitivity, specificity, positive predictive value, and negative predictive value were 79.65, 61.11, 81.08, and 58.93%, respectively. Compared with those without PAD, more patients with PAD had CIMT ≥0.71 mm (79.65 vs 38.89%; P&lt;0.001) and ICA plaques (66.37vs 11.11%; P&lt;0.001). Multivariate logistic regression revealed that age (odds ratio [OR]: 1.118; 95% confidence interval [95%CI]: 1.056–1.183; P&lt;0.001), ICA plaques (OR: 13.452; 95%CI: 4.450–40.662; P&lt;0.001), and CIMT ≥0.71 mm (OR: 2.802; 95%CI: 1.092–7.188; P=0.032) were associated with PAD.CIMT may be a surrogate marker of PAD in patients with DF.