Beatriz Julião Vieira Aarestrup

Effect of thalidomide and pentoxifylline on experimental autoimmune encephalomyelitis (EAE)

BACKGROUND Autoimmune encephalomyelitis (EAE) in Lewis rats is a classical experimental model of demyelinating inflammatory disease of the central nervous system. EAE is widely accepted for study of immune-inflammatory mechanisms in the CNS related to multiple sclerosis (MS) due to similar clinical evolution. OBJECTIVES In the present study we investigated the effects of Thalidomide and pentoxifylline during EAE development in Lewis rats. METHODS EAE was induced in Lewis rats and treatment with Thalidomide or pentoxifylline was performed. Clinical evaluation was carried out daily. Histopathological analysis of the brain tissue and spinal cord was performed. Griess method was used for determination of NO serum levels. TNF-alpha and IFN-gamma serum levels were investigated using ELISA method. RESULTS Thalidomide and pentoxifylline treatment is associated with significant reduction of neuroinflammation in CNS. Serum levels of NO, IFN-gamma and TNF-alpha showed a marked reduction. Such findings were correlated with improvement of clinical symptoms, particularly in thalidomide treated rats. CONCLUSIONS Taken together the data suggested that thalidomide and pentoxifylline may be therapeutic options for the treatment of MS, however further experiments must be performed to investigate this hypothesis.

Body weight gain and serum leptin levels of non-overweight and overweight/obese pregnant women

Background Our objective was to evaluate changes in serum leptin levels during pregnancy in overweight/obese and non-obese women and to assess total and percent weight gain during pregnancy as possible factors that influence leptin levels. Material/Methods In a prospective study of 42 low-risk pregnant women receiving prenatal care, we assessed serum leptin levels at gestational weeks 9–12, 25–28, and 34–37. Based on their pre-pregnancy body mass indices (BMIs), the cohort was divided into: non-overweight (BMI <25 kg/m2) and overweight/obese (BMI ≥25 kg/m2) subjects. Results We found a progressive increase in maternal weight gain during pregnancy in both groups. There was also a progressive increase in leptin levels in the 2 strata; however, the increase was significantly higher in the non-overweight patient group. We found that non-overweight pregnant women had a noticeably larger total weight gain. When analyzing the percent weight gain during pregnancy compared to the pre-pregnancy weight, the non-overweight group had a significantly greater percent weight gain than the overweight/obese group. Conclusions Our results suggest that the greater increase in leptin levels in non-overweight pregnant women can be explained by the higher percent weight gain in this group compared to overweight/obese women. These findings suggest that controlling the percent weight gain may be an important preventive measure when controlling leptin levels during pregnancy and subsequent medical complications.

Protective Effects of Baccharis dracunculifolia Leaves Extract against Carbon Tetrachloride- and Acetaminophen-Induced Hepatotoxicity in Experimental Animals

In this work we investigated the in vivo protective effects of Baccharis dracunculifolia leaves extract (BdE) against carbon tetrachloride (CCl4)- and acetaminophen (APAP)-induced hepatotoxicity. Total phenolic content, total flavonoid content, antioxidant DPPH radical scavenging activity, and HPLC analysis were performed. Our results showed that pretreatment with BdE significantly reduced the damage caused by CCl4 and APAP on the serum markers of hepatic injury, AST, ALT, and ALP. Results were confirmed by histopathological analysis. Phytochemical analysis, performed by HPLC, showed that BdE was rich in p-coumaric acid derivatives, caffeoylquinic acids and flavonoids. BdE also showed DPPH antioxidant activity (EC50 of 15.75 ± 0.43 μg/mL), and high total phenolic (142.90 ± 0.77 mg GAE/g) and flavonoid (51.47 ± 0.60 mg RE/g) contents. This study indicated that B. dracunculifolia leaves extract has relevant in vivo hepatoprotective properties.

Copaiba Oil Suppresses Inflammatory Cytokines in Splenocytes of C57Bl/6 Mice Induced with Experimental Autoimmune Encephalomyelitis (EAE)

Experimental autoimmune encephalomyelitis (EAE) is a murine autoimmune disease used to study multiple sclerosis. We have investigated the immunomodulatory effects of copaiba oil (100, 50 and 25 µg/mL) on NO, H2O2, TNF-α, IFN-γ and IL-17 production in cultured cells from EAE-mice. Copaiba oil (100 µg/mL) inhibited H2O2, NO, IFN-γ TNF-α and IL-17 production spontaneously or after ConA and MOG35–55 stimulation. It is suggested that copaiba oil acts on the mechanism of development of EAE by IFN-γ, IL-17 and TNF-α inhibition, modulating the immune response on both Th1 and Th17 cells.

Effects of aqueous extract of Echinodorus grandiflorus on the immune response in ovalbumin-induced pulmonary allergy

BACKGROUND Asthma is a disease characterized by intermittent obstruction of the airways and chronic inflammation that affects approximately 300 million people worldwide. The immune response in asthma is predominantly T(H)2, with high levels of total and allergen-specific IgE and bronchial eosinophilia. Asthma treatment is aimed at controlling the disease, and the drugs used currently have systemic adverse effects and generally are not effective in difficult-to-control cases. OBJECTIVE To investigate the effect of aqueous extract of Echinodorus grandiflorus, a plant used in folk medicine for its diuretic and anti-inflammatory properties, in a model of pulmonary allergy. METHODS BALB/c mice were intraperitoneally sensitized and nasally challenged with ovalbumin. Aqueous extract and dexamethasone treatments (0.1 mL/d per mouse) were initiated on day 32 and concluded on day 40. Eight hours after the last challenge evaluations, of serum, bronchoalveolar lavage, and lung tissue were performed. RESULTS Oral treatment with the extract markedly reduced the number of total cells and eosinophils in bronchoalveolar lavage. The eosinophil peroxidase activity in lung tissue, the levels of ovalbumin-specific IgE in serum, the levels of CCL11, and the gene expression of interleukin 4 and interleukin 13 in lung tissue were also lower after treatment. CONCLUSIONS These results suggest that the aqueous extract of E grandiflorus is able to modulate allergic pulmonary inflammation and may be useful as a potential therapeutic agent for asthma.

Fraction of exhaled nitric oxide measurements in the diagnoses of asthma in elderly patients

Objective To assess the value of fraction of exhaled nitric oxide (FeNO) measurements in the diagnosis of asthma in elderly patients. Methods The clinical symptoms of 202 elderly patients were assessed with the asthma module of the International Study of Asthma and Allergies in Childhood test, which had been modified for the elderly patients, and the diagnostic routine for chronic obstructive pulmonary disease (COPD), which was based on the Global initiative for chronic Obstructive Lung Disease criteria. Of the 202 patients assessed, 43 were subjected to pulmonary function evaluations (spirometry) and FeNO measurements. Results Of the 202 elderly patients, 34 had asthma (23 definite and eleven probable), 20 met COPD criteria, 13 presented with an overlap of asthma and COPD, and 135 did not fit the criteria for obstructive pulmonary disease. Among the 43 elderly patients who were subjected to FeNO measurements, ten showed altered results (23.2%) and 33 had normal results (76.7%). The average value of FeNO in patients with definite and probable asthma undergoing this procedure was 29.2 parts per billion whereas that in nonasthmatic patients was 17.5 parts per billion (P=0.0002). Conclusion We show a clear relationship between FeNO levels and asthma symptoms and previous asthma diagnoses in elderly patients.

Hyperoxia promotes polarization of the immune response in ovalbumin-induced airway inflammation, leading to a TH17 cell phenotype

Previous studies have demonstrated that hyperoxia‐induced stress and oxidative damage to the lungs of mice lead to an increase in IL‐6, TNF‐α, and TGF‐β expression. Together, IL‐6 and TGF‐β have been known to direct T cell differentiation toward the TH17 phenotype. In the current study, we tested the hypothesis that hyperoxia promotes the polarization of T cells to the TH17 cell phenotype in response to ovalbumin‐induced acute airway inflammation. Airway inflammation was induced in female BALB/c mice by intraperitoneal sensitization and intranasal introduction of ovalbumin, followed by challenge methacholine. After the methacholine challenge, animals were exposed to hyperoxic conditions in an inhalation chamber for 24 h. The controls were subjected to normoxia or aluminum hydroxide dissolved in phosphate buffered saline. After 24 h of hyperoxia, the number of macrophages and lymphocytes decreased in animals with ovalbumin‐induced airway inflammation, whereas the number of neutrophils increased after ovalbumin‐induced airway inflammation. The results showed that expression of Nrf2, iNOS, T‐bet and IL‐17 increased after 24 of hyperoxia in both alveolar macrophages and in lung epithelial cells, compared with both animals that remained in room air, and animals with ovalbumin‐induced airway inflammation. Hyperoxia alone without the induction of airway inflammation lead to increased levels of TNF‐α and CCL5, whereas hyperoxia after inflammation lead to decreased CCL2 levels. Histological evidence of extravasation of inflammatory cells into the perivascular and peribronchial regions of the lungs was observed after pulmonary inflammation and hyperoxia. Hyperoxia promotes polarization of the immune response toward the TH17 phenotype, resulting in tissue damage associated with oxidative stress, and the migration of neutrophils to the lung and airways. Elucidating the effect of hyperoxia on ovalbumin‐induced acute airway inflammation is relevant to preventing or treating asthmatic patients that require oxygen supplementation to reverse the hypoxemia.

Inibição da expressão de ciclooxigenase 2 em feridas cutâneas de camundongos NOD submetidos à terapia a laser de baixa intensidade

BACKGROUND: Low-level laser therapy (LLLT) has been reported to modulate the healing of wounds by inducing an increase in fibroblast number associated with increased expression of the cytokine transforming growth factor-β2 (TGF-β2). OBJECTIVE: In the present study, the effect of LLLT on expression of COX2 at the site of tissue repair was evaluated, using an experimental model with non obese diabetic mice (NOD) to study cutaneous wound healing. METHODS: Thirty NOD mice were used, of which 14 were diabetic and were divided into two groups: group I (n=7) underwent a surgical procedure of skin wounds and group II (n=7) underwent a surgical procedure of skin wounds and treated with LLLT. Group II was submitted to LLLT in the following parameters: 15 mW of power, dose of 3.8 J/cm2 and exposure time of 20 seconds. Seven days after surgery and after laser application, animals were euthanized with an overdose of anesthesia and tissue samples were collected for subsequent histological analysis, histomorphometry and immunohistochemistry. RESULTS: The LLLT has promoted the inhibition of COX2 expression in skin wounds in mice diabetic. Taken together the results suggest that LLLT modulate the expression of COX2 improved the control of inflammatory reaction in cutaneous wound lesions in NOD mice. CONCLUSION: Taken together, the results suggested that LLLT is able to negatively modulate the expression of COX2 enzyme contributing to the inflammatory response in cutaneous wounds in NOD mice.

β-Caryophyllene ameliorates the development of experimental autoimmune encephalomyelitis in C57BL/6 mice

Multiple sclerosis is the most common autoimmune inflammatory and demyelinating disease of the central nervous system. The experimental autoimmune encephalomyelitis (EAE) is an appropriate and a well-establish model for studying the pathogenesis of MS. β-caryophyllene (BCP), a natural sesquiterpene found in many plant species, is a potent anti-inflammatory compound. Herein we investigated the in vitro and in vivo immunomodulatory effects of BCP on C57BL/6 mice induced with EAE. BCP was in vitro evaluated (4, 20, and 40μM) on splenocytes obtained from EAE-induced C57BL/6 mice, and in vivo (25 or 50mg/kg/day) orally administered on EAE-mice. The clinical course, body weight, cytokines and oxygen radicals production were investigated in C57BL/6 EAE-mice. In vitro and in vivo immunological responses were evaluated by ELISA, and CNS sections were stained by hematoxylin and eosin methods The in vitro production of H2O2, NO, IFN-γ, and TNF- α was inhibited by BCP (20 and 40μM) in cultured cells from EAE-mice. BCP (25 and 50mg/kg/day) reduced clinical score and severity of EAE and inhibited H2O2, NO, TNF-α, IFN-γ and, IL-17 production. EAE-mice, orally treated with BCP (mainly at 50mg/kg/day), displayed levels of cytokines and clinical signs similar to animals with no EAE disease, demonstrating the therapeutic action of BCP on EAE animals. Histopathological and histomorphometric analysis confirmed that BCP treatment significantly reduced the numbers of inflammatory infiltrates and attenuated neurological damages in the CNS of EAE-mice.

Circunferência abdominal avaliada antes da 12ª semana de gestação: correlação com níveis séricos de leptina

PURPOSE: To evaluate the correlation between maternal waist circumference measured before the 12th week of gestation and serum leptin levels during pregnancy, as well as to compare the leptin levels of women with and without abdominal obesity diagnosed in early pregnancy. METHODS: Prospective study including 40 pregnant women receiving low-risk prenatal care, older than 20 years, nonsmokers, with singleton pregnancies and without chronic disease. Waist circumference was measured before the 12th week and serum leptin levels were measured between the 9th and 12th, 25th and 28th and 34th and 37th weeks of gestation. According to waist circumference measurement, the cohort was divided into two groups: with and without abdominal obesity. The Mann-Whitney and χ2 tests were used to assess the differences between groups. The Pearson correlation coeffient was used to assess the association between waist circumference and serum leptin levels during pregnancy. The level of significance was set at p<0.05. RESULTS: The mean weight and body mass index of patients with abdominal obesity (74.4±11.0 kg/28.9±4.1) was higher than that of patients without abdominal obesity (55.6±5.9 kg/21.1±2.4) (p=0.001). The mean leptin levels in pregnant patients with abdominal obesity (41.9±3.5 ng/mL) was higher than in patients without abdominal obesity (23.6±2.7 ng/mL) (p<0.0002). A positive correlation was obtained between the waist circumference measured during the same period and the mean serum leptin levels (r=0.7; p<0.0001). CONCLUSIONS: Waist circumference measured before the 12th week of pregnancy is a valid and simple method to predict the serum leptin levels throughout pregnancy. Pregnant women with abdominal obesity diagnosed before 12th week have higher mean serum leptin levels during pregnancy than those without abdominal obesity.