Abstract in English:

Distal convoluted tubules (DCT), which contain the Na-Cl cotransporter (NCC) inhibited by thiazide diuretics, undergo complex modulation to preserve Na+ and K+ homeostasis. The lysine kinases 1 and 4 (WNK1 and WNK4), identified as hyperactive in the hereditary disease pseudohypoaldosteronism type 2, are responsible for activation of NCC and consequent hypokalemia and hypertension. WNK4, highly expressed in DCT, activates the SPAK/OSR1 kinases, which phosphorylate NCC and other regulatory proteins and transporters in the distal nephron. WNK4 works as a chloride sensor through a Cl- binding site, which acts as an on/off switch at this kinase in response to changes of basolateral membrane electrical potential, the driving force of cellular Cl- efflux. High intracellular Cl- in hyperkalemia decreases NCC phosphorylation and low intracellular Cl- in hypokalemia increases NCC phosphorylation and activity, which makes plasma K+ concentration a central modulator of NCC and of K+ secretion. The WNK4 phosphorylation by cSrc or SGK1, activated by angiotensin II or aldosterone, respectively, is another relevant mechanism of NCC, ENaC, and ROMK modulation in states such as volume reduction, hyperkalemia, and hypokalemia. Loss of NCC function induces upregulation of electroneutral NaCl reabsorption by type B intercalated cells through the combined activity of pendrin and NDCBE, as demonstrated in double knockout mice (KO) animal models, Ncc/pendrin or Ncc/NDCBE. The analysis of ks-Nedd-4-2 KO animal models introduced the modulation of NEDD4-2 by intracellular Mg2+ activity as an important regulator of NCC, explaining the thiazide-induced persistent hypokalemia.

Abstract in English:

Borderline personality disorder (BPD) is a severe psychiatric condition that affects up to 2.7% of the population and is highly linked to functional impairment and suicide. Despite its severity, there is a lack of knowledge about its pathophysiology. Studies show genetic influence and childhood violence as factors that may contribute to the development of BPD; however, the involvement of neuroinflammation in BPD remains poorly investigated. This article aimed to explore the pathophysiology of BPD according to the levels of brain-derived neurotrophic factor (BDNF), inflammatory cytokines, and oxidative stress substances that exacerbate neuronal damage. Few articles have been published on this theme. They show that patients with BPD have a lower level of BDNF and a higher level of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in peripheral blood, associated with increased plasma levels of oxidative stress markers, such as malondialdehyde and 8-hydroxy-2-deoxyguanosine. Therefore, more research on the topic is needed, mainly with a pre-clinical and clinical focus.

Abstract in English:

Immuno-oncology studies the immune system in cancer. In recent decades, immunotherapy has shown a good response to the treatment of various locally advanced and metastatic cancers. The main mechanisms of action include stimulation of the patient's own immune system to enhance immune responses acting in tumor escape pathways. This review examined the literature related to immune system mechanisms in head and neck squamous cell carcinoma (HNSCC) and their application in immunotherapy using biomarkers. The PUBMED, LILACS, MEDLINE, WHOLIS, and SCIELO databases were searched using the terms squamous cell carcinoma, head and neck, immuno-oncology, immunotherapy, and immunology. The main drugs currently available for clinical use in patients diagnosed with HNSCC include pembrolizumab and nivolumab, both classified as check-point inhibitors. These immunobiological agents improve patient survival and quality of life. Many authors and clinical trials point out that the recommendation of these agents is linked to the dose of PD-L1 (ligand expressed primarily by tumor cells), which proved to be an unreliable biomarker in the patient selection. Recommendation of immunotherapy depends on reliable biomarkers that must be identified in order to achieve good therapeutic results.

Abstract in English:

Procainamide (PA) and its in vivo metabolite, N-acetylprocainamide (NAPA), display some pharmacological differences. Although it is agreed that PA is a class IA antiarrhythmic, it has been reported that NAPA is a pure class III antiarrhythmic that affects only the repolarizing phase of the cardiac action potential. This last concept, observed exclusively in dogs, gained wide acceptance, appearing in classic pharmacology textbooks. However, evidence in species such as mice and rats indicates that NAPA can affect cardiac Na+ channels, which is unexpected for a pure class III antiarrhythmic drug. To further clarify this issue, the effects of PA (used as a reference drug) and NAPA on the maximum upstroke velocity (Vmax) and half-decay time (HDT) of the cardiac action potential were examined in the isolated right papillaris magnus of the guinea pig heart. Both PA and NAPA affected Vmax at lower concentrations than required to affect HDT, and NAPA had weaker effects on both variables. Thus, NAPA displayed typical class IA antiarrhythmic behavior. Therefore, the concept that NAPA is a pure class III antiarrhythmic drug is more species-dependent than previously envisioned. In addition, we demonstrated that the differential pharmacology of PA and NAPA is explainable, in molecular terms, by steric hindrance of the effects of NAPA and the greater number of potent aromatic-aromatic and cation π interactions with Na+ or K+ cardiac channels for PA.

Abstract in English:

Gelsolin (GSN) can sever actin filaments associated with autophagy. This study investigated how GSN-regulated actin filaments control autophagy in pancreatic ductal epithelial cells (PDECs) in acute pancreatitis (AP). AP was produced in a rat model and PDECs using caerulein (CAE). Rat pancreatic duct tissue and HPDE6-C7 cells were extracted at 6, 12, 24, and 48 h after CAE treatment. HPDE6-C7 cells in the presence of CAE were treated with cytochalasin B (CB) or silenced for GSN for 24 h. Pancreatic histopathology and serum amylase levels were analyzed. Cellular ultrastructure and autophagy in PDECs were observed by transmission electron microscopy after 24 h of CAE treatment. The expression of GSN and autophagy markers LC3, P62, and LAMP2 was evaluated in PDECs by immunohistochemistry and western blotting. Actin filaments were observed microscopically. Amylase levels were highest at 6 h of AP, and pancreatic tissue damage increased over time. Mitochondrial vacuolization and autophagy were observed in PDECs. CAE increased GSN expression in these cells over time, increased the LC3-II/LC3-I ratio and LAMP2 expression at 24 and 6 h of treatment, respectively, and decreased P62 expression at all time points. CB treatment for 24 h decreased the LC3-II/LC3-I ratio and LAMP2 expression, increased P62 levels, but had no impact on GSN expression in CAE-treated PDECs. CAE induced actin depolymerization, and CB potentiated this effect. GSN silencing increased the LC3-II/LC3-I ratio and LAMP2 expression and reduced actin depolymerization in CAE-treated PDECs. GSN may inhibit autophagosome biogenesis and autophagosome-lysosome fusion by increasing actin depolymerization in PDECs in AP.

Abstract in English:

There is a high demand for stroke rehabilitation in the Brazilian public health system, but most studies that have addressed rehabilitation for unilateral spatial neglect (USN) after stroke have been performed in high-income countries. Therefore, the aim of this study was to analyze USN patient recruitment in a multicenter noninvasive brain stimulation clinical trial performed in Brazil and to provide study design recommendations for future studies. We evaluated the reasons for exclusion of patients from a multicenter, randomized, double-blinded clinical trial of rehabilitation of USN patients after stroke. Clinical and demographic variables were compared between the included and excluded patients. A descriptive statistical analysis was performed. Only 173 of the 1953 potential neglect patients (8.8%) passed the initial screening. After screening evaluation, 87/173 patients (50.3%) were excluded for clinical reasons. Cognitive impairment led to the exclusion of 21/87 patients (24.1%). Low socioeconomic status led to the exclusion of 37/173 patients (21.4%). Difficulty obtaining transportation to access treatment was the most common reason for their exclusion (16/37 patients, 43.3%). The analyzed Brazilian institutions have potential for conducting studies of USN. The recruitment of stroke survivors with USN was restricted by the study design and limited financial support. A history of cognitive impairment, intracranial stenting or craniectomy, and lack of transportation were the most common barriers to participating in a multicenter noninvasive brain stimulation trial among patients with USN after stroke.

Abstract in English:

Diabetes affects every tissue in the body, including the skin. The main skin problem is the increased risk of infections, which can lead to foot ulcers. Most studies evaluating the effects of diabetes on the skin are carried out in wound healing areas. There are fewer studies on uninjured skin, and some particularities of this tissue are yet to be elucidated. In general, cellular and molecular outcomes of diabetes are increased oxidative stress and lipid peroxidation. For our study, we used C57BL/6 mice that were divided into diabetic and non-diabetic groups. The diabetic group received low doses of streptozotocin on 5 consecutive days. To evaluate the effects of hyperglycemia on uninjured skin, we performed morphological analysis using hematoxylin/eosin staining, cellular analysis using Picrosirius red and Nissl staining, and immunostaining, and evaluated protein expression by polymerase chain reaction. We confirmed that mice were hyperglycemic, presenting all features related to this metabolic condition. Hyperglycemia caused a decrease in interleukin 6 (Il-6) and an increase in tumor necrosis factor alpha (Tnf-α), Il-10, F4/80, tumor growth factor beta (Tgf-β), and insulin-like growth factor 1 (Igf-1). In addition, hyperglycemia led to a lower cellular density in the epidermis and dermis, a delay in the maturation of collagen fibers, and a decrease in the number of neurons. Furthermore, we showed a decrease in Bdnf expression and no changes in Ntrk2 expression in the skin of diabetic animals. In conclusion, chronic hyperglycemia in mice induced by streptozotocin caused disruption of homeostasis even before loss of skin continuity.

Abstract in English:

Functional constipation (FC) is one of the most common gastrointestinal disorders characterized by hard stools and infrequent bowel movements, which is associated with dysfunction of the enteric nervous system and intestinal motility. Luteolin, a naturally occurring flavone, was reported to possess potential pharmacological activities on intestinal inflammation and nerve injury. This study aimed to explore the role of luteolin and its functional mechanism in loperamide-induced FC mice. Our results showed that luteolin treatment reversed the reduction in defecation frequency, fecal water content, and intestinal transit ratio, and the elevation in transit time of FC models. Consistently, luteolin increased the thickness of the muscular layer and lessened colonic histopathological injury induced by loperamide. Furthermore, we revealed that luteolin treatment increased the expression of neuronal protein HuC/D and the levels of intestinal motility-related biomarkers, including substance P (SP), vasoactive intestinal polypeptide (VIP), and acetylcholine (ACh), as well as interstitial cells of Cajal (ICC) biomarker KIT proto-oncogene, receptor tyrosine kinase (C-Kit), and anoctamin-1 (ANO1), implying that luteolin mediated enhancement of colonic function and contributed to the anti-intestinal dysmotility against loperamide-induced FC. Additionally, luteolin decreased the upregulation of aquaporin (AQP)-3, AQP-4, and AQP-8 in the colon of FC mice. In summary, our data showed that luteolin might be an attractive option for developing FC-relieving medications.

Abstract in English:

Determining outcomes and predictors of mortality following discharge from tuberculosis (TB) hospitalization is crucial to establish health policies. The objective of this study was to analyze outcomes and, secondarily, predictors of mortality following discharge from TB hospitalization. This was a prospective cohort study of patients diagnosed with TB (all forms) discharged from the hospital who began treatment during hospitalization. Out of 169 subjects included, 38 died during the 13-months of follow-up, within a median of 3 months (95%CI: 1.49-4.51). In the multivariate analysis, the variables independently associated with death were age (HR=1.04, 95%CI: 1.01-1.06, P=0.001), presence of sputum production (HR=2.18, 95%CI: 1.09-4.34, P=0.027), and Charlson Comorbidity Index (HR=1.19, 95%CI: 1.04-1.36, P=0.015). In conclusion, post-discharge mortality in subjects hospitalized for TB was 22.5%, with mean survival of 4.6 months. The mortality was higher in older subjects, in those who reported sputum production, and in those with a high comorbidity index.

Abstract in English:

The systematic assessment of cognitive performance of older people without cognitive complaints is controversial and unfeasible. Identifying individuals at higher risk of cognitive impairment could optimize resource allocation. We aimed to develop and test machine learning models to predict cognitive impairment using variables obtainable in primary care settings. In this cross-sectional study, we included 8,291 participants of the baseline assessment of the ELSA-Brasil study, who were aged between 50 and 74 years and were free of dementia. Cognitive performance was assessed with a neuropsychological battery and cognitive impairment was defined as global cognitive z-score below 2 standard deviations. Variables used as input to the prediction models included demographics, social determinants, clinical conditions, family history, lifestyle, and laboratory tests. We developed machine learning models using logistic regression, neural networks, and gradient boosted trees. Participants' mean age was 58.3±6.2 years, 55% were female. Cognitive impairment was present in 328 individuals (4%). Machine learning algorithms presented fair to good discrimination (areas under the ROC curve between 0.801 and 0.873). Extreme Gradient Boosting presented the highest discrimination, high specificity (97%), and negative predictive value (97%). Seventy-six percent of the individuals with cognitive impairment were included among the highest ranked individuals by this algorithm. In conclusion, we developed and tested a machine learning model to predict cognitive impairment based on primary care data that presented good discrimination and high specificity. These characteristics could support the detection of patients who would not benefit from cognitive assessment, facilitating the allocation of human and economic resources.

Abstract in English:

Upper and lower limbs can be affected by several diseases and changes related to current life habits, such as the sedentarism, technological advances, and even eating habits. This cross-sectional study investigated morphological adaptations of the biceps brachii muscle and the performance of the elbow flexors in healthy individuals in the early phase of aging. Thirty-two volunteers were separated according to age range (3rd, 4th, and 5th decades of life) and sex. Smaller diameters and subtypes of fibers were evaluated using muscle biopsies, and peak torque and total work were assessed using an isokinetic dynamometer. The variables were compared considering sex and decade, using mixed-effects linear models. The smaller diameter of all fiber types did not differ significantly between age groups for either sex. The proportion of oxidative fibers was reduced in male participants in the 4th (-20%) and 5th (-6%) decades of life compared to the 3rd decade, and there was an increase in the number of oxidative fibers in women from the 4th (+14%) to the 5th decade of life. There were no significant changes in the peak torque and total work between the analyzed age groups. The early phase of aging starts with alterations in the proportion of fibers, with a decrease in oxidative fibers in men and an increase in oxidative fibers in women. Smaller diameter, torque, and total work did not change over these decades of life.

Abstract in English:

Globally, cardiac arrest (CA) is a leading cause of death and disability. Asphyxial CA (ACA)-induced kidney damage is a crucial factor in reducing the survival rate. The purpose of this study was to investigate the role of antioxidant enzymes in histopathological renal damage in an ACA rat model at different time points. A total of 88 rats were divided into five groups and exposed to ACA except for the sham group. To evaluate glomerular function and oxidative stress, serum levels of blood urea nitrogen (BUN) and creatinine (Crtn) and malondialdehyde (MDA) levels in renal tissues were measured. To determine histopathological damage, hematoxylin and eosin staining, periodic acid-Schiff staining, and Masson's trichrome staining were performed. Expression levels of antioxidant enzymes including superoxide dismutase-1 (SOD-1), superoxide dismutase-2 (SOD-2), catalase (CAT), and glutathione peroxidase (GPx) were measured by immunohistochemistry (IHC). Survival rate of the experimental rats was reduced to 80% at 6 h, 55% at 12 h, 42.9% at 1 day, and 33% at 2 days after return of spontaneous circulation. Levels of BUN, Crtn, and MDA started to increase significantly in the early period of CA induction. Renal histopathological damage increased markedly from 6 h until two days post-CA. Additionally, expression levels of antioxidant enzymes were significantly decreased at 6 h, 12 h, 1 day, and 2 days after CA. CA-induced oxidative stress and decreased levels of antioxidant enzymes (SOD-1, SOD-2, CAT, GPx) from 6 h to two days could be possible mediators of severe renal tissue damage and increased mortality rate.

Abstract in English:

The expression of T-type voltage-dependent Ca2+ channels (Cav3) has been previously observed in breast cancer, but their expression and subcellular localization were not evaluated in pre-neoplastic lesions. Therefore, this work aimed to evaluate protein expression and subcellular localization of T-type channel isoforms in human breast tissue samples. Protein expressions of CaV3.1, CaV3.2, and CaV3.3 were evaluated by immunohistochemistry in breast without alteration, in proliferative non-neoplastic lesions, and in neoplastic ductal epithelial lesions of the human breast. CaV3.1, CaV3.2, and CaV3.3 nuclear expressions were decreased in advanced stages of neoplastic transformation, whereas CaV3.1 and CaV3.2 cytoplasmic expression increased. Also, the decrease in nuclear expression was correlated with an increase in cytoplasmic expression for CaV3.1 isoform. The change in CaV3 protein expression and subcellular localization are consistent with the neoplastic transformation stages of mammary epithelial cells, evident in early neoplastic lesions, such as ductal carcinomas in situ. These results suggest a possible involvement of CaV3 in the carcinogenic processes and could be considered as a potential pharmacological target in new therapies for breast cancer treatment.

Abstract in English:

Current data shows that the autonomic and vascular systems can influence each other. However, only a few studies have addressed this association in the general population. We aimed to investigate whether heart rate variability (HRV) was associated with coronary artery calcium (CAC) in a cross-sectional analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). We examined baseline data from 3138 participants (aged 35 to 74 years) without previous cardiovascular disease who underwent CAC score assessment and had validated HRV recordings. Prevalent CAC was defined as a CAC score>0, and HRV analyses were performed over 5-min segments. We detected CAC score>0 in 765 (24.4%) participants. Subgroup analyses in older participants (≥49 years) adjusted for sociodemographic and clinical variables revealed that CAC score>0 was associated with lower values of standard deviation of NN intervals (SDNN) (odds ratio [OR]=1.32; 95%CI: 1.05,1.65), root mean square of successive differences between adjacent NN intervals (RMSSD) (OR=1.28; 95%CI: 1.02,1.61), and low frequency (LF) (OR=1.53, 95%CI: 1.21,1.92). Interaction analysis between HRV indices and sex in age-stratified groups revealed significant effect modification: women showed increased OR for prevalent CAC in the younger group, while for men, the associations were in the older group. In conclusion, participants aged ≥49 years with low SDNN, RMSSD, and LF values were more likely to present prevalent CAC, suggesting a complex interaction between these markers in the pathogenesis of atherosclerosis. Furthermore, our results suggested that the relationship between CAC and HRV might be sex- and age-related.

Abstract in English:

The purinergic system participates in the control of blood pressure. Hypertension promotes the occurrence of gastrointestinal disorders such as intestinal inflammation and gastric emptying delay. This study aimed i) to investigate the participation of the P2X7 receptor blocker Brilliant Blue G (BBG) on gastric emptying of solids and changes in oxidative stress in the gastric fundus, duodenum, and colon of spontaneously hypertensive rats (SHR) and ii) to study the putative relationship of this effect with the renin-angiotensin system. Rats were divided into five groups: Control, SHR, SHR+BBG, SHR+BBG+ATP, and SHR+BBG+ANG II. In the gastrointestinal tract, we assessed gastric emptying (GE) and oxidative stress markers (NOx, MPO, GSH, SOD). We observed a decrease in the GE rate (P<0.05) in SHR vs control rats (21.8±2.0% vs 42.8±3.5%). The decrease in GE was returned (P<0.05) to control levels by BBG in SHR rats (21.8±2.0% vs 41.6±3.2%). Co-administration of ATP or ANG II together with BBG bypassed the effect of the P2X7 antagonist on GE in SHR (P<0.05) (21.9±5.0% vs 25.6±3.0% vs 41.6±3.2%). The MPO activity increased (P<0.05) in the gastric fundus of SHR compared to control rats (6.12±2.26 vs 0.077±0.02 UMPO/mg tissue); this effect was prevented (P<0.05) by BBG (0.55±0.15 vs 6.12±2.26 UMPO/mg tissue). Data demonstrated that blockage of P2X7 receptors with BBG can improve the GE delay and oxidative stress biomarkers in SHR animals. This preventive effect of BBG on GE delay was abrogated by ANG II and ATP, thus prompting crosstalk between renin-angiotensin and the purinergic signaling systems underlying this phenomenon.

Abstract in English:

Amyloid fibrils are characteristic of several disorders including Alzheimer's disease (AD), with no cure or preventive therapy. Diminishing amyloid deposits using aromatic compounds is an interesting approach toward AD treatment. The present study examined the anti-fibrillogenic effects of silibinin and trans-chalcone in vitro, in vivo, and in silico on insulin amyloids. In vitro incubation of insulin at 37°C for 24 h induced amyloid formation. Addition of trans-chalcone and silibinin to insulin led to reduced amounts of fibrils as shown by thioflavin S fluorescence and Congo red absorption spectroscopy, with a better effect observed for silibinin. In vivo bilateral injection of fibrils formed by incubation of insulin in the presence or absence of silibinin and trans-chalcone or insulin fibrils plus the compounds in rats' hippocampus was performed to obtain AD characteristics. Passive avoidance (PA) test showed that treatment with both compounds efficiently increased latency compared with the model group. Histological investigation of the hippocampus in the cornu ammonis (CA1) and dentate gyrus (DG) regions of the rat's brain stained with hematoxylin-eosin and thioflavin S showed an inhibitory effect on amyloid aggregation and markedly reduced amyloid plaques. In silico, a docking experiment on native and fibrillar forms of insulin provided an insight onto the possible binding site of the compounds. In conclusion, these small aromatic compounds are suggested to have a protective effect on AD.

Abstract in English:

The longitudinal association between psoriasis and carotid intima-media thickness (CIMT) has not yet been established. This study aimed do compare CIMT and its change (∆CIMT) after an 8-year follow-up according to psoriasis diagnosis and the association with risk factors in the ELSA-Brasil study. Data from 7564 participants were analyzed (median age of 50.0 [44.0-57.0] years, 56.9% women). CIMT was assessed by ultrasound and ∆CIMT was calculated by subtracting baseline values from follow-up values. Psoriasis participants were identified by self-reported medical diagnosis (n=143) and compared with matched participants without disease (n=572) and with the entire sample without psoriasis (n=7421). Baseline CIMT explained the 8-year CIMT increase only in 36.9% among psoriasis participants and in ∼43.0% in participants without disease. CIMT was associated with age (β=0.002, P=0.002) and hypertension (β=0.029, P=0.034) in psoriasis participants. Among participants without psoriasis, CIMT was associated with age, male sex, low educational attainment, past smoking, obesity, diabetes, hypertension, and dyslipidemia (P<0.05). There was an inverse association of CIMT with private health insurance (β=-0.004, P=0.042) and White ethnicity (β=-0.006, P=0.004) in the entire sample without psoriasis but not in matched participants. Psoriasis participants showed an inverse association between ∆CIMT and diabetes (β=-0.214, P=0.011), while the entire sample without psoriasis showed an inverse association between ∆CIMT and age (β=-0.005, P<0.001), past smoking (β=-0.048, P=0.009), and hypertension (β=-0.048, P=0.009). In conclusion, psoriasis was not associated with CIMT after an 8-year follow-up. The inverse association of ∆CIMT with diabetes in psoriasis participants needs further clarification.

Abstract in English:

Oxidative stress plays a role in the delay of peripheral nerve regeneration after injury. The accumulation of free radicals results in nerve tissue damage and dorsal root ganglion (DRG) neuronal death. Pinostrobin (PB) is one of the bioflavonoids from Boesenbergia rotunda and has been reported to possess antioxidant capacity and numerous pharmacological activities. Therefore, this study aimed to investigate the effects of PB on peripheral nerve regeneration after injury. Male Wistar rats were randomly divided into 5 groups including control, sham, sciatic nerve crush injury (SNC), SNC + 20 mg/kg PB, and SNC + 40 mg/kg PB. Nerve functional recovery was observed every 7 days. At the end of the study, the sciatic nerve and the DRG were collected for histological and biochemical analyses. PB treatment at doses of 20 and 40 mg/kg reduced oxidative stress by up-regulating endogenous glutathione. The reduced oxidative stress in PB-treated rats resulted in increased axon diameters, greater number of DRG neurons, and p-ERK1/2 expression in addition to faster functional recovery within 4 weeks compared to untreated SNC rats. The results indicated that PB diminished the oxidative stress-induced nerve injury. These effects should be considered in the treatment of peripheral nerve injury.

Abstract in English:

Ethanol is a central nervous system depressant that is widely consumed worldwide. When consumed chronically, it may have several consequences to the organism, such as oxidative stress. Ethanol metabolism increases the production of oxidant molecules and its consumption may cause changes in enzymatic and non-enzymatic systems that maintain cellular homeostasis. The activity of endogenous enzymes and lipid peroxidation are altered in alcohol consumers. Therefore, this study aimed to evaluate oxidative stress parameters in ethanol users compared to a control group. For that, the activity of the enzymes superoxide dismutase, catalase, and glutathione peroxidase, the ferric reducing/antioxidant power (FRAP), and malondialdehyde were evaluated. The influence of the amount of ethanol consumed on the analyzed parameters was also verified. The group of alcohol users consisted of 52 volunteers, 85% male and 15% female, with a mean age of 41±13 years. The control group consisted of 50 non-drinkers, 40% male and 60% female, with a mean age of 50±10 years. There was a significant difference in superoxide dismutase (P<0.001) and malondialdehyde (P=0.007) measurements between groups, as both parameters were increased in the group of ethanol users. Because of the higher amount of ethanol consumed, there was an increase of the catalase activity parameters and gradual reduction of FRAP. Thus, the ethanol-consuming participants were most likely under oxidative stress.

Abstract in English:

The use of routine magnetic resonance imaging (MRI) to potentially assess skeletal fragility has been widely studied in osteoporosis. The aim of this study was to evaluate bone texture attributes (TA) from routine lumbar spine (LS) MRI and their correlation with vertebral fragility fractures (VFF) and bone mineral density (BMD). Sixty-four post-menopausal women were submitted to LS densitometry, total spine radiographs, and routine T2-weighted LS MRI. Twenty-two TA were extracted with the platform IBEX from L3 vertebra. The statistical difference was evaluated using ANOVA and Duncan's post-test. Correlation analyses were performed using Spearman's coefficient. Statistical significance was considered when P<0.05. The results did not show a significant difference in BMD between the women with and without fractures. Two bone TA (cluster tendency and variance) were significantly lower in the fracture group. Cluster tendency with VFF in osteopenia was 1.54±1.37 and in osteoporosis was 1.11±58. Cluster tendency without VFF in osteopenia was 2.23±1.38 and in osteoporosis was 1.88±1.14). Variance with VFF in osteopenia was 1.44±1.37 and in osteoporosis was 1.13±59. Variance without VFF in osteopenia was 2.34±1.38 and in osteoporosis was 1.89±1.14. There was a significant correlation between BMD and cluster prominence (r=0.409), cluster tendency (r=0.345), correlation (r=0.570), entropy (r=0.364), information measure corr1 (r=0.378), inverse variance (r=0.449), sum entropy (r=0.320), variance (r=0.338), sum average (r=-0.274), and sum variance (r=-0.266). Our results demonstrated the potential use of TA extracted from routine MRI as a biomarker to assess osteoporosis and identify the tendency of skeletal fragility vertebral fractures.

Abstract in English:

Liver injury occurs after ischemia and reperfusion (IR), as seen in transplant settings. Sex hormones have been implicated in many pathophysiological mechanisms in females and this could lead to liver protection under inflammatory reperfusion conditions where an excessive immune response occurs. Despite such assumptions, this fact needs to be further investigated. To address this, female and male C57BL/6J mice (8-12 weeks old) were studied. Bilateral ovariectomy (OVX) was performed in females to decrease estradiol levels. IR was performed, and after two weeks, all animals underwent a sham control operation or IR with euthanasia at the following time points after reperfusion: 6, 12, 24, and 48 h. IR triggered an inflammatory process in the liver with recruitment of neutrophils into the parenchyma of male mice. The female sham mice were protected against liver IR presenting no alteration of aminotransferase (ALT) levels compared to males. OVX caused loss of protection, increasing hepatic injury as represented by increased ALT levels and myeloperoxidase (MPO) activity. Female sham mice showed increased Akt phosphorylation and activation, while males showed reduced Akt activation. Estradiol pretreatment recovered ALT levels after IR injury, which was associated with decreased liver injury.

Abstract in English:

Chronic nonspecific low back pain (CNLBP) is the most common musculoskeletal condition, which can be influenced by nociceptive, psychosocial, cognitive, and affective aspects, causing vulnerabilities and impairing the individual's ability to manage pain. The association of continuous shortwave diathermy (CSWD) with Pilates-based exercises may contribute to reduce pain, depression, and anxiety in patients with CNLBP. A single-blind randomized clinical trial was performed in which 36 patients with CNLBP were divided into a control group that received placebo CSWD and an intervention group that received active CSWD. Both groups received 12 sessions of Pilates-based exercises. Pain, depression, and anxiety variables were evaluated using the McGill questionnaire, the Beck Depression Inventory, and the Visual Analog Anxiety Scale. Assessments were performed at baseline, after three and six weeks of treatment, and at the three-month follow-up. The Shapiro-Wilk test, Student's t-test, Mann-Whitney U test, chi-squared test, and repeated measures ANOVA, with α=0.05, were used to compare the outcomes, and indicated that active CSWD did not present additional improvement in the assessed variables in CNLBP patients compared to the placebo group. Both groups improved pain and depression at follow-up and reduced anxiety only during Pilates-based exercises. Therefore, only Pilates-based exercises seemed sufficient to manage patients with CNLBP.

Abstract in English:

Chronic intermittent hypoxia (CIH), a component of sleep apnea-hypopnea syndrome, is suggested to cause damage to lung tissue, and the role of glutamate is not well studied. We used a chronic long-term intermittent hypobaric hypoxia (CLTIHH) model of rats to find out if such procedure causes lung injury and the potential effect of N-methyl-D-aspartate receptors (NMDARs) by using receptor antagonist MK-801 (dizocilpine). Thirty-two rats were placed into four groups; a control and three CLTIHH groups where rats were placed into a low-pressure chamber set to 430 mmHg for 5 h/day, 5 days/week, for 5 weeks. Only one group received MK-801 (0.3 mg/kg, ip) daily. We evaluated tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and nuclear factor (NF)-kB for the inflammatory process, superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPX), total antioxidant status (TAS), and total oxidant status (TOS) for oxidative stress, and caspase-9 levels. Blood plasma, bronchoalveolar fluid (BALF), and lung tissue extracts were evaluated. Both oxidant and inflammatory parameters were significantly increased in all the mediums of the CLTIHH groups except the group that received MK-801. Significant evidence was collected on MK-801 alleviating the effect of CLTIHH. Histological evaluations revealed lung damage and fibrotic changes in the CLTIHH groups. It was first shown that the CLTIHH procedure caused chronic lung injury, and that inflammation and oxidant stress were influential in the formation of lung injury. Secondly, NMDAR antagonist MK-801 effectively inhibited the development of lung injury and fibrosis.

Abstract in English:

The main goal of this study was to determine whether oxidative imbalance mediated by AT1 receptor (AT1R) is responsible for deleterious endothelial responses to mental stress (MS) in overweight/obese class I men. Fifteen overweight/obese men (27±7 years old; 29.8±2.6 kg/m2) participated in three randomized experimental sessions with oral administration of the AT1R blocker olmesartan (40 mg; AT1R blockade) or ascorbic acid (AA; 3g) infusion or placebo [both intravenously (0.9% NaCl) and orally]. After two hours, endothelial function was determined by flow-mediated dilation (FMD) before (baseline), 30 min (30MS), and 60 min (60MS) after a five-minute acute MS session (Stroop Color Word Test). Blood was collected before (baseline), during MS, and 60 min after MS for redox homeostasis profiling: lipid peroxidation (TBARS; thiobarbituric acid reactive species), protein carbonylation, and catalase activity by colorimetry and superoxide dismutase (SOD) activity by an ELISA kit. At the placebo session, FMD significantly decreased 30MS (P=0.05). When compared to baseline, TBARS (P<0.02), protein carbonylation (P<0.01), catalase (P<0.01), and SOD (P<0.01) increased during the placebo session. During AT1R blockade, FMD increased 30 min after MS (P=0.01 vs baseline; P<0.01 vs placebo), while AA infusion increased FMD only 60 min after MS. No differences were observed during MS with the AT1R blockade and AA regarding TBARS, protein carbonylation, catalase, and SOD. AT1R-mediated redox imbalances played an important role in endothelial dysfunction to mental stress.

Abstract in English:

In biliary atresia (BA), efforts to prevent premature liver transplantation (LT) are aimed at early diagnosis, timing of Kasai-portoenterostomy (KPE), and centralization of care. This report presents the clinical picture, treatment strategies, and outcomes of BA patients with no previous treatment. A retrospective cohort study (Jan/2001 to Jan/2021) was conducted to evaluate the outcome of patients with BA referred to a single team. Study groups were: 1) Kasai-only group (K-only) n=9), 2) LT-only group (n=7), and 3) Kasai+LT group (K+LT) (n=23). Survival with native liver and overall survival were 22.9 and 94.8%, respectively, at 120 months of follow-up. There was no difference in age at KPE in the K-only group (46.8±21.8 days) vs K+LT (52.1±22 days), P=0.4. Ten (25.6%) patients were babies conceived through in vitro fertilization (IVF). Four IVF patients (40%) presented associated congenital heart disease vs 5 patients (17%) in the remaining group (P=0.14). Two of the IVF patients were premature (<37 weeks). Median maternal age at birth was 35 years (33 to 41 years). Excellent patient survival is expected for patients with BA with the available treatment strategies. IVF+BA was an unexpected prevalent association in this cohort, and further studies are required to better understand these findings.