Rafael Vercelino

Redox signalling and the inflammatory response in rheumatoid arthritis

Reactive oxygen species (ROS) are produced mainly during oxidative phosphorylation and by activated phagocytic cells during oxidative burst. The excessive production of ROS can damage lipids, protein, membrane and nucleic acids. They also serve as important intracellular signalling that enhances the inflammatory response. Many studies have demonstrated a role of ROS in the pathogenesis of inflammatory chronic arthropathies, such as rheumatoid arthritis. It is known that ROS can function as a second messenger to activate nuclear factor kappa‐B, which orchestrates the expression of a spectrum of genes involved in the inflammatory response. Therefore, an understanding of the complex interactions between these pathways might be useful for the development of novel therapeutic strategies for rheumatoid arthritis.

Quercetin Administration Ameliorates Pulmonary Complications of Cirrhosis in Rats

In the hepatopulmonary syndrome (HPS), a common complication of liver cirrhosis, pulmonary endothelial endothelin B (ETB) receptor overexpression, enhanced endothelial nitric oxide (NO) synthase (eNOS)-derived NO production, and increases in pulmonary inducible NO synthase (iNOS) and heme oxygenase (HO-1) are important factors in the development of vasodilatation. These changes may be influenced by redox-sensitive signaling pathways, including nuclear factor-kappaB (NF-kappaB). In this study, our aim was to evaluate the effects of the flavonoid antioxidant quercetin on the development of HPS in rats with common bile duct ligation (CBDL). Rats were divided into the following 4 groups: rats subjected to CBDL, Sham (rats subjected to simulated CBDL), quercetin-treated sham, and quercetin-treated CBDL. Quercetin (50 mg/kg) was administered for 2 wk starting on d 14 after surgery. Increased NO production, overexpression of iNOS, eNOS, HO-1, and ETB-receptor and activation of NF-kappaB were observed in lung of CBDL rats. Quercetin inhibited oxidative stress, NF-kappaB activation, and the expression of different pulmonary mediators involved in HPS. Quercetin also ameliorated liver injury and reduced the expression of hepatic endothelin-1 and HO-1 in untreated cirrhotic rats. Our findings suggest that quercetin administered after the onset of hepatic injury significantly ameliorates pulmonary complications in CBDL rats and that limitation of cirrhotic evolution contributes to this effect.

N-Acetylcysteine Effects on Genotoxic and Oxidative Stress Parameters in Cirrhotic Rats with Hepatopulmonary Syndrome

The aim of this study was to evaluate the potential antioxidant effects of N-acetylcysteine in hepatopulmonary syndrome, a complication of cirrhosis, using an experimental model of common bile duct ligation in rats. Male Wistar rats were divided into four experimental groups: CBDL (animals submitted to common bile duct ligation); Sham (animals submitted to simulated common bile duct ligation); Sham + N-acetylcysteine, and CBDL + N-acetylcysteine. N-acetylcysteine (10 mg/kg, intraperitoneally) was administered for 2 weeks starting on day 14 after surgery. Some alterations in the liver integrity were investigated by evaluation of serum enzymes aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and arterial blood gases. Lipoperoxidation by thiobarbituric acid-reactive substances assay, superoxide dismutase activity and total nitrates was measured as parameters of oxidative stress, performed on lung homogenates. Micronucleus assay in bone marrow and comet assay in lung, liver and blood were performed to assess the genotoxic effects by oxidative stress. The results showed an improvement in the enzymatic parameters and arterial blood gases, a reduction of lipoperoxidation and in the total nitrates after treatment with N-acetylcysteine. Histological analysis showed vasodilatation in the lung, which was reversed by N-acetylcysteine. Micronuclei frequency and DNA damage in lung and liver were increased in the CBDL group. N-Acetylcysteine caused no genotoxic effect and did not influence the induction of micronucleus in bone marrow and DNA damage in lung and liver. The results suggest protective effects after treatment with N-acetylcysteine in cirrhotic rats with hepatopulmonary syndrome.

Ligadura de ducto biliar como modelo de estudo da síndrome hepatopulmonar e estresse oxidativo

BACKGROUND The hepatopulmonary syndrome is characterized by hepatic dysfunction and presence of dilated pulmonary vessels, with alterations in air diffusion that can be demonstrated in the experimental model of common bile duct ligation. AIM To evaluate the oxidative stress in pulmonary tissue of cirrhotic rats with common bile duct ligation. MATERIAL/METHODS We used 12 male Wistar rats weighing between 200-300 g divided in two groups: control (Co = 6) and cirrhotic (Ci = 6). We evaluated aminotransferases, arterial gasometry, lipoperoxidation and chemoluminescence), and antioxidant enzymatic activity with superoxide dismutase. The tissues analyzed for hepatopulmonary syndrome were cirrhotic liver and lung. RESULTS The animals with common bile duct ligation showed alterations in the following aminotransferases: aspartate aminotransferase, Co = 105.3 +/- 43/Ci = 500.5 +/- 90.3, alanine aminotransferase, Co = 78.75 +/- 37.7/Ci = 162.75 +/- 35.4, and alkaline phosphatase, Co = 160 +/- 20.45/Ci = 373 +/- 45.44. The lipoperoxidation and the antioxidant response had significant differences between the groups when evaluated in lung (lipoperoxidation) Co = 0.87 +/- 0.3/Ci = 2.01 +/- 0.9, chemoluminescence Co = 16008.41 +/- 1171.45/Ci = 20250.36 +/- 827.82 superoxide dismutase Co = 6.66 +/- 1.34/Ci = 16.06 +/- 2.67. CONCLUSIONS Our results suggest that in this experimental model of cirrhosis using common bile duct ligation, there is an increase in lipoperoxidation in pulmonary tissue as well as an increase in superoxide dismutases antioxidant activity, suggesting a pulmonary injury caused by secondary biliary cirrhosis.

Transcranial direct current stimulation (tDCS) reverts behavioral alterations and brainstem BDNF level increase induced by neuropathic pain model: Long-lasting effect

INTRODUCTION Neuropathic pain (NP) is a chronic pain modality that usually results of damage in the somatosensory system. NP often shows insufficient response to classic analgesics and remains a challenge to medical treatment. The transcranial direct current stimulation (tDCS) is a non-invasive technique, which induces neuroplastic changes in central nervous system of animals and humans. The brain derived neurotrophic factor plays an important role in synaptic plasticity process. Behavior changes such as decreased locomotor and exploratory activities and anxiety disorders are common comorbidities associated with NP. OBJECTIVE Evaluate the effect of tDCS treatment on locomotor and exploratory activities, and anxiety-like behavior, and peripheral and central BDNF levels in rats submitted to neuropathic pain model. METHODS Rats were randomly divided: Ss, SsS, SsT, NP, NpS, and NpT. The neuropathic pain model was induced by partial sciatic nerve compression at 14 days after surgery; the tDCS treatment was initiated. The animals of treated groups were subjected to a 20 minute session of tDCS, for eight days. The Open Field and Elevated Pluz Maze tests were applied 24 h (phase I) and 7 days (phase II) after the end of tDCS treatment. The serum, spinal cord, brainstem and cerebral cortex BDNF levels were determined 48 h (phase I) and 8 days (phase II) after tDCS treatment by ELISA. RESULTS The chronic constriction injury (CCI) induces decrease in locomotor and exploratory activities, increases in the behavior-like anxiety, and increases in the brainstem BDNF levels, the last, in phase II (one-way ANOVA/SNK, P<0.05 for all). The tDCS treatment already reverted all these effects induced by CCI (one-way ANOVA/SNK, P<0.05 for all). Furthermore, the tDCS treatment decreased serum and cerebral cortex BDNF levels and it increased these levels in the spinal cord in phase II (one-way ANOVA/SNK, P<0.05). CONCLUSION tDCS reverts behavioral alterations associated to neuropathic pain, indicating possible analgesic and anxiolytic tDCS effects. tDCS treatment induces changes in the BDNF levels in different regions of the central nervous system (CNS), and this effect can be attributed to different cellular signaling activations.

Long-Lasting Effect of Transcranial Direct Current Stimulation in the Reversal of Hyperalgesia and Cytokine Alterations Induced by the Neuropathic Pain Model

BACKGROUND Neuropathic pain (NP) is caused by an insult or dysfunction in the peripheral or central nervous system (CNS), the main symptoms being mechanical allodynia and hyperalgesia. NP often shows insufficient response to classic analgesics and its management remains a challenge. Transcranial direct current stimulation (tDCS) is a non-invasive method of cerebral stimulation and represents a promising resource for pain management. OBJECTIVE/HYPOTHESIS We investigated the effects of tDCS on the nociceptive response and on IL-1β, IL-10, and TNF-α levels in CNS structures of rats with NP. METHODS After induction of NP by chronic constriction injury (CCI) of the sciatic nerve, the rats received 20 min of bicephalic tDCS for 8 days. Hyperalgesia was assessed by the hot plate and von Frey tests and evaluated at baseline, 7 days, and 14 days after CCI surgery, and also immediately, 24 hours, and 7 days following tDCS treatment. The levels of IL-1β, IL-10 and TNF-α in the cortex, spinal cord, and brainstem were determined by ELISA at 48 hours and 7 days post-tDCS. RESULTS The CCI model provoked thermal and mechanical hyperalgesia until at least 30 days post-CCI; however, bicephalic tDCS relieved the nociceptive behavior for up to 7 days after treatment completion. CONCLUSIONS Bicephalic tDCS is effective to promote antinociceptive behavior in neuropathic pain, which can be reflected by a spinal neuroimmunomodulation linked to pro- and anti-inflammatory cytokine levels observed in the long-term.

Avaliação da força muscular respiratória e da função pulmonar em pacientes com insuficiência cardíaca

BACKGROUND: Heart failure (HF) is the inability of the heart to pump enough blood to supply the necessities of the body. Pulmonary function and respiratory muscles can be affected and typical symptoms presented by the patients include discomfort at a minimal exertion. OBJECTIVE: To verify pulmonary function and respiratory muscle strength in patients with class II and III HF as defined by the New York Heart Association (NYHA). METHODS: The study was descriptive and observational, and comprised 12 class II and III HF patients in follow-up at the out-patient. Pulmonary function assessments [Forced Expiratory Volume in the first second (FEV1) and Forced Vital Capacity (FVC)] were performed using microspirometry and respiratory muscle strength [Maximal Expiratory Pressure (MEPmax) and Maximal Inspiratory Pressure (MIPmax)] were evaluated using a pressure transducer (Globalmed™). RESULTS: Differences were found between the functional classes II and III in relation to pulmonary function: FEV1 (II: 91.17±19.87; III: 68.17±21.78); FVC (II: 68.17±21.78; III: 73.67±22.94); and respiratory muscle strength: MIPmax (II: 71.67±40.70; III: 53.33±29.27) and MEPmax (II: 98.83±34.56; III: 58.33±15.06). The class II were higher for all study parameters, only MEPmax revealed a statistically significant difference. CONCLUSION: The pulmonary function and respiratory muscle strength are impaired in heart failure patients class III patients, particularly in relation to MEPmax.

Effects of acupuncture on the symptoms of anxiety and depression caused by premenstrual dysphoric disorder

Objective The objective of this investigation was to evaluate the effects of acupuncture and sham acupuncture on the symptoms of anxiety and depression brought on by premenstrual dysphoric disorder (PMDD). Methods In a single-blind randomised clinical trial, 30 volunteers with PMDD were assigned alternately to group 1 (acupuncture) or group 2 (sham acupuncture), and completed an evaluation of symptoms of anxiety and depression using the Hamilton Anxiety (HAM-A) and Hamilton Depression (HAM-D) Rating Scales. The procedure was performed twice a week for two menstrual cycles, for a total of 16 attendances for each participant. Results Before the intervention the mean HAM-A and HAM-D scores did not differ between groups. Following the intervention symptoms of anxiety and depression were reduced in both groups; however, the improvement was significant in group 1 compared to group 2, as shown by a mean reduction in HAM-A scores of 58.9% in group 1 and 21.2% in group 2 (p<0.001). The reduction in the mean HAM-D scores was 52.0% in group 1 and 19.6% in group 2, resulting in a significant difference (p=0.012). Conclusions The results suggest that acupuncture could be another treatment option for PMDD patients.

Influência de processos redox na resposta inflamatória da artrite reumatóide

Reactive oxygen species (ROS) are produced mainly during the oxidative phosphorylation and by activated phagocytic cells during oxidative burst.The excessive production of ROS can damage lipids, protein, membrane and nucleic acids. They also serve as important intracellular signaling that amplify the inflammatory response. A lot of studies have demonstrated an role of ROS in the pathogenesis of inflammatory chronic artropathy, such as rheumatoid arthritis. It is known that an ROS can function as a second messenger to stimulate nuclear factor kappa-B that orchestrate the expression of a spectrum of genes that perpetuate an inflammatory response. Therefore, an understanding of the complex interactions between these pathways might be useful for the development of novel therapeutics strategies for rheumatoid artritis.

Effectiveness of acupuncture combined with rehabilitation for treatment of acute or subacute stroke: a systematic review

Objectives To determine whether the combination of acupuncture and rehabilitation produces better results in the treatment of acute or subacute stroke sequelae than rehabilitation alone. Methods A systematic review was carried out. A search was conducted in March 2014 using PubMed, Medline, the Cochrane Library, Chinese National Knowledge Infrastructure database (CNKI) and Wanfang databases. English and Chinese language articles published within 10 years of the search were reviewed for inclusion. Randomised control trials comparing combined treatment with acupuncture and rehabilitation and rehabilitation alone in patients with acute or subacute stroke (onset until 3 months after stroke) were included in this review. Three review authors independently checked the titles and abstracts of trials for inclusion based on selection criteria. Studies measuring changes of motor function, activities of daily living, neurological deficit or spasticity/range of motion during the treatment period and at the end of follow-up were included. Results 17 trials met the inclusion criteria, of which five were of good quality. 14 trials had results favourable to acupuncture combined with rehabilitation, compared with conventional rehabilitation treatment alone. Conclusions Acupuncture in combination with rehabilitation may have benefits for the treatment of acute and subacute stroke sequelae in comparison with rehabilitation alone. However, many of the studies were at risk of bias. Future studies should focus on reaching a consensus about the most appropriate modality of acupuncture intervention, and the appropriate length of treatment for both interventions, to maximise the potential synergistic outcomes.