Scielo RSS <![CDATA[Brazilian Journal of Medical and Biological Research]]> vol. 50 num. 4 lang. pt <![CDATA[SciELO Logo]]> <![CDATA[A novel frameshift mutation of Chediak-Higashi syndrome and treatment in the accelerated phase]]> Chediak-Higashi syndrome (CHS) is a rare autosomal recessive immunodeficiency disease characterized by frequent infections, hypopigmentation, progressive neurologic deterioration and hemophagocytic lymphohistiocytosis (HLH), known as the accelerated phase. There is little experience in the accelerated phase of CHS treatment worldwide. Here, we present a case of a 9-month-old boy with continuous high fever, hypopigmentation of the skin, enlarged lymph nodes, hepatosplenomegaly and lung infection. He was diagnosed with CHS by gene sequencing, and had entered the accelerated phase. After 8 weeks of therapy, the boy had remission and was prepared for allogenic stem cell transplantation. <![CDATA[Overexpression of ezrin and galectin-3 as predictors of poor prognosis of cervical cancer]]> The aim of this study was to explore the correlation of ezrin and galectin-3 expressions with prognosis in cervical cancer. The immunohistochemical method was applied to detect ezrin and galectin-3 expressions in normal cervix tissues (n=30), cervicitis tissues (n=28), cervical intraepithelial neoplasia (CIN) tissues (classified as I-III, n=89), and cervical carcinoma tissues (n=84). Follow-up was conducted for 5 to 78 months to analyze the correlation of protein expressions with prognosis. Ezrin and galectin-3 expressions in cervical cancer were significantly higher than in normal cervix, cervicitis and CIN (all P&lt;0.05), and expressions in CIN were significantly higher than in normal cervix and cervicitis (both P&lt;0.05). The expressions of ezrin and galectin-3 were both related with histological grade, deep myometrial invasion and lymph node metastasis (all P&lt;0.05). Spearman analysis showed that ezrin expression was positively correlated with galectin-3 expression in cervical cancer (r=0.355, P&lt;0.05). The survival rate of patients with high expressions of ezrin and galectin-3 was significantly lower than those with low expressions of proteins (both P&lt;0.05). The expressions of ezrin and galectin-3, histological grade, depth of stromal invasion, and lymph node metastasis are risk factors affecting the survival rate of patients with cervical cancer. The expressions of ezrin and galectin-3 were correlated with the development of cervical cancer, and overexpressions of those proteins were indicative of poor prognosis in patients with cervical cancer. <![CDATA[CIRBP protects H9C2 cells against myocardial ischemia through inhibition of NF-κB pathway]]> Myocardial ischemia is a major cause of death and remains a disease with extremely deficient clinical therapies and a major problem worldwide. Cold inducible RNA-binding protein (CIRBP) is reported to be involved in multiple pathological processes, including myocardial ischemia. However, the molecular mechanisms of myocardial ischemia remain elusive. Here, we first overexpressed CIRBP by transfection of pc-CIRBP (pcDNA3.1 containing coding sequenced for CIRBP) and silenced CIRBP by transfection of small interfering RNA targeting CIRBP (siCIRBP). pcDNA3.1 and the negative control of siCIRBP (siNC) were transfected into H9C2 cells to act as controls. We then constructed a cell model of myocardial ischemia through culturing cells in serum-free medium with hypoxia in H9C2 cells. Subsequently, AlamarBlue assay, flow cytometry and western blot analysis were used, respectively, to assess cell viability, reactive oxygen species (ROS) level and apoptosis, and expression levels of IκBα, p65 and Bcl-3. We demonstrated that CIRBP overexpression promoted cell proliferation (P&lt;0.001), inhibited cell apoptosis (P&lt;0.05), reduced ROS level (P&lt;0.001), down-regulated phosphorylated levels of IκBα and p65 (P&lt;0.01 or P&lt;0.001), and up-regulated expression of Bcl-3 (P&lt;0.001) in H9C2 cells with myocardial ischemia. The influence of CIRBP knockdown yielded opposite results. Our study revealed that CIRBP could protect H9C2 cells against myocardial ischemia through inhibition of NF-κB pathway. <![CDATA[Naringenin regulates production of matrix metalloproteinases in the knee-joint and primary cultured articular chondrocytes and alleviates pain in rat osteoarthritis model]]> Inflammation of cartilage is a primary symptom for knee-joint osteoarthritis. Matrix metalloproteinases (MMPs) are known to play an important role in the articular cartilage destruction related to osteoarthritis. Naringenin is a plant-derived flavonoid known for its anti-inflammatory properties. We studied the effect of naringenin on the transcriptional expression, secretion and enzymatic activity of MMP-3 in vivo in the murine monosodium iodoacetate (MIA) osteoarthritis model. The assessment of pain behavior was also performed in the MIA rats. The destruction of knee-joint tissues was analyzed microscopically. Moreover, the effect of naringenin was also studied in vitro in IL-1β activated articular chondrocytes. The transcriptional expression of MMP-3, MMP-1, MMP-13, thrombospondin motifs (ADAMTS-4) and ADAMTS-5 was also studied in primary cultured chondrocytes of rats. Naringenin caused significant reduction in pain behavior and showed marked improvement in the tissue morphology of MIA rats. Moreover, a significant inhibition of MMP-3 expression in MIA rats was observed upon treatment with naringenin. In the in vitro tests, naringenin caused a significant reduction in the transcriptional expression, secretion and enzymatic activity of the studied degradative enzymes. The NF-κB pathway was also found to be inhibited upon treatment with naringenin in vitro. Overall, the study suggests that naringenin alleviated pain and regulated the production of matrix-metalloproteinases via regulation of NF-κB pathway. Thus, naringenin could be a potent therapeutic option for the treatment of osteoarthritis. <![CDATA[Influence of antihypertensive drugs on aortic and coronary effects of Ang-(1-7) in pressure-overloaded rats]]> This study investigated the influence of antihypertensive drugs, such as angiotensin-converting enzyme inhibitors (ACEIs), AT1 receptor blockers (ARBs), voltage-gated L-type calcium channel blockers, and mineralocorticoid receptor antagonists (MRAs), on the effects of angiotensin-(1-7) [Ang-(1-7)] on aorta and coronary arteries from pressure-overloaded rats. Pressure overload was induced by abdominal aortic banding (AB). To evaluate the role of antihypertensive drugs on the effect of Ang-(1-7), AB male Wistar rats weighing 250–300 g were treated with vehicle or low doses (5 mg·kg-1·day-1, gavage) of losartan, captopril, amlodipine, or spironolactone. Isolated aortic rings and isolated perfused hearts under constant flow were used to evaluate the effect of Ang-(1-7) in thoracic aorta and coronary arteries, respectively. Ang-(1-7) induced a significant relaxation in the aorta of sham animals, but this effect was reduced in the aortas of AB rats. Chronic treatments with losartan, captopril or amlodipine, but not with spironolactone, restored the Ang-(1-7)-induced aorta relaxation in AB rats. The coronary vasodilatation evoked by Ang-(1-7) in sham rats was blunted in hypertrophic rats. Only the treatment with losartan restored the coronary vasodilatory effect of Ang-(1-7) in AB rat hearts. These data support a beneficial vascular effect of an association of Ang-(1-7) and some antihypertensive drugs. Thus, this association may have potential as a new therapeutic strategy for cardiovascular diseases. <![CDATA[Cerebral blood flow and vasoreactivity in aging: an arterial spin labeling study]]> Regional cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) in young and elderly participants were assessed using pulsed arterial spin labeling (ASL) and blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) techniques in combination with inhalation of CO2. Pulsed ASL and BOLD-MRI were acquired in seventeen asymptomatic volunteers (10 young adults, age: 30±7 years; 7 elderly adults, age: 64±8 years) with no history of diabetes, hypertension, and neurological diseases. Data from one elderly participant was excluded due to the incorrigible head motion. Average baseline CBF in gray matter was significantly reduced in elderly (46±9 mL·100 g-1·min-1) compared to young adults (57±8 mL·100 g-1·min-1; P=0.02). Decreased pulsed ASL-CVR and BOLD-CVR in gray matter were also observed in elderly (2.12±1.30 and 0.13±0.06 %/mmHg, respectively) compared to young adults (3.28±1.43 and 0.28±0.11 %/mmHg, respectively; P&lt;0.05), suggesting some degree of vascular impairment with aging. Moreover, age-related decrease in baseline CBF was observed in different brain regions (inferior, middle and superior frontal gyri; precentral and postcentral gyri; superior temporal gyrus; cingulate gyri; insula, putamen, caudate, and supramarginal gyrus). In conclusion, CBF and CVR were successfully investigated using a protocol that causes minimal or no discomfort for the participants. Age-related decreases in baseline CBF and CVR were observed in the cerebral cortex, which may be related to the vulnerability for neurological disorders in aging. <![CDATA[Influence of schooling and age on cognitive performance in healthy older adults]]> Few studies have examined the influence of a low level of schooling on age-related cognitive decline in countries with wide social and economic inequalities by using the Cambridge Automated Neuropsychological Test Battery (CANTAB). The aim of the present study was to assess the influence of schooling on age-related cognitive decline using unbiased cognitive tests. CANTAB allows cognitive assessment across cultures and education levels with reduced interference of the examiner during data acquisition. Using two-way ANOVA, we assessed the influences of age and education on test scores of old adults (61–84 years of age). CANTAB tests included: Visual Sustained Attention, Reaction Time, Spatial Working Memory, Learning and Episodic Memory. All subjects had a minimum visual acuity of 20/30 (Snellen Test), no previous or current history of traumatic brain/head trauma, stroke, language impairment, chronic alcoholism, neurological diseases, memory problems or depressive symptoms, and normal scores on the Mini Mental State Examination (MMSE). Subjects were grouped according to education level (1 to 7 and ≥8 years of schooling) and age (60–69 and ≥70 years). Low schooling level was associated with significantly lower performance on visual sustained attention, learning and episodic memory, reaction time, and spatial working memory. Although reaction time was influenced by age, no significant results on post hoc analysis were detected. Our findings showed a significantly worse cognitive performance in volunteers with lower levels of schooling and suggested that formal education in early life must be included in the preventive public health agenda. In addition, we suggest that CANTAB may be useful to detect subtle cognitive changes in healthy aging. <![CDATA[Therapy of tacrolimus combined with corticosteroids in idiopathic membranous nephropathy]]> We evaluated the efficacy and safety of tacrolimus (TAC) combined with corticosteroids in treating patients with idiopathic membranous nephropathy (IMN). One hundred seventy-seven biopsy-proven IMN patients were recruited in this retrospective clinical study. Sixty patients received TAC (target blood concentration of 4–8 ng/mL) and 117 patients received daily cyclophosphamide (CYC, 100 mg) combined with prednisone. Remission rates at the end of the first, second and third month in the TAC group were significantly higher than that in the CYC group (1st: 35.0 vs 19.7%, P&lt;0.05; 2nd: 56.7 vs 38.5%, P&lt;0.05; 3rd: 76.7 vs 59.0%, P&lt;0.05). In the first 3 months, daily urinary protein and serum albumin in the TAC group obtained a better improvement than that in the CYC group (P&lt;0.05). At the end of the sixth and the twelfth month, the remission rates, daily urinary protein and serum albumin were all comparable between the two groups (P&gt;0.05). No significant difference of relapse rate between the groups was found (16.3 vs 12.0%, P&gt;0.05). Patients were more likely to develop glucose intolerance in the TAC group. The TAC regimen obtained more benefits in treating IMN patients, especially in the first 3 months, than the CYC regimen.