Does cotinine act upon reactive oxygen species and peroxidases?

Nicotine, an oxidizing agent, is certainly one of the most widely used alkaloids in the world. It is, together with its main metabolite, cotinine, responsible for tobacco-dependence. The use of tobacco is closely associated with lung disease, morphological leukocyte modification and generation of oxidant species. The aim of this study was to look for a possible relationship between cotinine, oxidant species generation and oxidative processes. After studying the action of cotinine in some chemical oxidation models and on the enzymatic kinetics of peroxidases (myeloperoxidase and horseradish peroxidase), we concluded that cotinine does not act directly upon H 2O 2, HOCl, taurine chloramines, horseradish peroxidase or myeloperoxidase.

Harmonic, reactive and unbalance compensation by means of CPT framework

This paper presents possible selective current compensation strategies based on the Conservative Power Theory (CPT). This recently proposed theory, introduces the concept of complex power conservation under non-sinusoidal conditions. Moreover, the related current decompositions results in several current terms, which are associated with a specific physical phenomena (power absorption P, energy storage Q, voltage and current distortion D). Such current components are used in this work for the definition of different current compensators, which can be selective in terms of minimizing particular disturbing effects. The choice of one or other current component for compensation directly affects the sizing and cost of active and/or passive devices and it will be demonstrated that it can be done to attend predefined limits for harmonic distortion, unbalances and/or power factor. Single and three-phase compensation strategies will be discussed by means of the CPT Framework. Simulation and experimental results will be demonstrated in order to validate their performance. © 2009 IEEE.

Gene expression changes associated with myocarditis and fibrosis in hearts of mice with chronic chagasic cardiomyopathy

Chronic chagasic cardiomyopathy is a leading cause of heart failure in Latin American countries. About 30% of Trypanosoma cruzi-infected individuals develop this severe symptomatic form of the disease, characterized by intense inflammatory response accompanied by fibrosis in the heart.We performed an extensive microarray analysis of hearts from a mouse model of this disease and identified significant alterations in expression of ~12% of the sampled genes. Extensive up-regulations were associated with immune-inflammatory responses (chemokines, adhesion molecules, cathepsins, and major histocompatibility complex molecules) and fibrosis (extracellular matrix components, lysyl oxidase, and tissue inhibitor of metalloproteinase 1). Our results indicate potentially relevant factors involved in the pathogenesis of the disease that may provide newtherapeutic targets in chronic Chagas disease. © 2010 by the Infectious Diseases Society of America.

Practical comparisons among electronic energy meters, a precision energy meter and IEEE1459 for reactive energy measurements, under unbalanced and non-sinusoidal conditions

This paper presents a practical experimentation for comparing reactive/non-active energy measures, considering three-phase four-wire non-sinusoidal and unbalanced circuits, involving five different commercial electronic meters. The experimentation set provides separately voltage and current generation, each one with any waveform involving up to fifty-first harmonic components, identically compared with acquisitions obtained from utility. The experimental accuracy is guaranteed by a class A power analyzer, according to IEC61000-4-30 standard. Some current and voltage combination profiles are presented and confronted with two different references of reactive/non-active calculation methodologies; instantaneous power theory and IEEE 1459-2010. The first methodology considers the instantaneous power theory, present into the advanced mathematical internal algorithm from WT3000 power analyzer, and the second methodology, accomplish with IEEE 1459-2010 standard, uses waveform voltage and current acquisition from WT3000 as input data for a virtual meter developed on Mathlab/Simulink software. © 2012 IEEE.

Pathological and behavioral risk factors for higher serum c-reactive protein concentrations in free-living adults - A Brazilian community-based study

Low-grade chronic systemic inflammation is often associated with chronic non-communicable diseases, and its most frequently used marker, the C-reactive protein (CRP), has become an identifier of such diseases as well as an independent predictor for cardiovascular disorders and mortality. CRP is produced in response to pro-inflammatory signaling and to individual and behavioral factors, leading to pathological states. The aim of this study was to rank the predicting factors of high CRP concentrations in free-living adults from a community-based sample. We evaluated 522 adults (40-84 years old; 381 women) for anthropometric characteristics, dietary intake, clinical and physical tests, and blood analysis. Subjects were assigned to groups, according to CRP concentrations, as normal CRP (G1;<3.0 mg/L; n = 269), high CRP (G2; 3.0-6.0 mg/L; n = 139), and very high CRP (G3; >6.0 mg/dL; n = 116). Statistical comparison between groups used one-way ANOVA or Kruskal-Wallis tests, and prediction of altered values in increasing CRP was evaluated by proportional hazard models (odds ratio). CRP distribution was influenced by gender, body mass index, body and abdominal fatness, blood leukocytes, and neutrophil counts. The higher CRP group was discriminated by the above variables in addition to lower VO2max, serum metabolic syndrome components (triglycerides, glucose, and HDL cholesterol), higher insulin, homeostasis assessment of insulin resistance, uric acid, gamma-GT, and homocysteine. After adjustments, only fatness, blood leukocytes, and hyperglycemia remained as independent predictors for increased serum CRP concentrations. Intervention procedures to treat low-grade chronic inflammation in overweight women would mainly focus on restoring muscle mass and functions in addition to an antioxidant-rich diet. © 2012 Springer Science+Business Media, LLC.

Three-year follow-up of Interleukin 6 and C-reactive protein in chronic obstructive pulmonary disease

Background: Past studies have shown that mean values of Interleukin-6 (IL-6) and C-reactive protein (CRP) do not change significantly in COPD patients over a one-year period. However, longer period follow-up studies are still lacking. Thus, the aim of this study is to evaluate plasma CRP and IL-6 concentration over three years in COPD patients and to test the association between these inflammatory mediators and disease outcome markers. Methods: A cohort of 77 outpatients with stable COPD was evaluated at baseline, and 53 (mean FEV1, 56% predicted) were included in the prospective study. We evaluated Interleukin-6 (IL-6), C-reactive protein (CRP), six-minute walking distance (6MWD), and body mass index (BMI) at baseline and after three years. Plasma concentration of IL-6 was measured by high sensitivity ELISA, and CRP was obtained by high sensitivity particle-enhanced immunonephelometry. Results: IL-6 increased significantly after 3 years compared to baseline measurements [0.8 (0.5-1.3) vs 2.4 (1.3-4.4) pg/ml; p < 0.001] and was associated with worse 6MWD performance. In the Cox regression, increased IL-6 at baseline was associated with mortality [Hazard Ratio (95% CI) = 2.68 (0.13, 1.84); p = 0.02]. CRP mean values did not change [5 (1.6-7.9) vs 4.7 (1.7-10) pg/L; p = 0.84], although eleven patients (21%) presented with changes >3 mg/L in CRP after 3 years. Conclusions: The systemic inflammatory process, evaluated by IL-6, seems to be persistent, progressive and associated with mortality and worse physical performance in COPD patients. Trial registration: No.:NCT00605540. © 2013 Ferrari et al; licensee BioMed Central Ltd.

Use of algorithms for semi-automatic quantification of pulmonary fibrosis and emphysema

Obtaining a semi-automatic quantification of pathologies found in the lung, through images of high resolution computed tomography (HRCT), is of great importance to aid in medical diagnosis. Paraccocidioidomycosis (PCM) is a systemic disease that affects the lung and even after effective treatment leaves sequels such as pulmonary fibrosis and emphysema. It is very important to the area of tropical diseases that the lung injury be quantified more accurately. In this stud, we propose the development of algorithms in computational environment Matlab® able to objectively quantify lung diseases such as fibrosis and emphysema. The program consists in selecting the region of interest (ROI), and through the use of density masks and filters, obtaining the lesion area quantification in relation to the healthy area of the lung. The proposed method was tested on 15 exams of HRCT of patients with confirmed PCM. To prove the validity and effectiveness of the method, we used a virtual phantom, also developed in this research. © 2013 Springer-Verlag.

Major components of energy drinks (caffeine, taurine, and guarana) exert cytotoxic effects on human neuronal SH-SY5Y cells by decreasing reactive oxygen species production

Scope. To elucidate the morphological and biochemical in vitro effects exerted by caffeine, taurine, and guarana, alone or in combination, since they are major components in energy drinks (EDs). Methods and Results. On human neuronal SH-SY5Y cells, caffeine (0.125-2 mg/mL), taurine (1-16 mg/mL), and guarana (3.125-50 mg/mL) showed concentration-dependent nonenzymatic antioxidant potential, decreased the basal levels of free radical generation, and reduced both superoxide dismutase (SOD) and catalase (CAT) activities, especially when combined together. However, guarana-treated cells developed signs of neurite degeneration in the form of swellings at various segments in a beaded or pearl chain-like appearance and fragmentation of such neurites at concentrations ranging from 12.5 to 50 mg/mL. Swellings, but not neuritic fragmentation, were detected when cells were treated with 0.5 mg/mL (or higher doses) of caffeine, concentrations that are present in EDs. Cells treated with guarana also showed qualitative signs of apoptosis, including membrane blebbing, cell shrinkage, and cleaved caspase-3 positivity. Flow cytometric analysis confirmed that cells treated with 12.5-50 mg/mL of guarana and its combinations with caffeine and/or taurine underwent apoptosis. Conclusion. Excessive removal of intracellular reactive oxygen species, to nonphysiological levels (or antioxidative stress), could be a cause of in vitro toxicity induced by these drugs. © 2013 Fares Zeidán-Chuliá et al.

Prevalence of ∆F508, G551D, G542X, and R553X mutations among cystic fibrosis patients in the North of Brazil

ABSTRACT: Cystic fibrosis (CF) is the most common genetic disease among Caucasians and is rare among sub-Saharan Africans. The Brazilian population is not ethnically homogeneous but it is the result of three-way ethnic admixture of Europeans, Africans and Amerindians in varying proportions, depending on the region. In the present study, we investigated 33 patients who had been diagnosed and are currently under treatment for CF at the University Hospital João de Barros Barreto, Belém, Pará State. The molecular analysis for G542X, G551D and R553X mutations was performed by PCR followed by RFLP using BstNI, HincII and MboI, respectively, in polyacrylamide gel eletrophoresis and stained with AgNO3. The DF508 mutation (a deletion of 3 bp) was only analyzed by polyacrylamide gel electrophoresis and stained with AgNO3. Each sample was analyzed for regions of interest in the CFTR gene using amplified by PCR and specific primers. The DF508 and G551D mutations presented frequencies of 22.7 and 3%, respectively. In 74.3% of the remaining patients, none of the mutations investigated was found. The present study characterized in a sample of patients with an established clinical diagnosis of CF (asthma, repeated bronchopneumonia, disorders of nutritional status, etc.) the most frequent mutation ( DF508) in the North region of Brazil and is also the first report of the G551D mutation. In spite of the wide spectrum of CF mutations and the heterogeneous ethnic origin of the Amazon population, the molecular diagnosis is a helpful additional tool for the diagnosis and treatment of CF patients.

C-reactive protein and vasospasm after aneurysmal subarachnoid hemorrhage1

PURPOSE:To evaluate the relationship between C reactive protein levels and clinical and radiological parameters with delayed ischemic neurological deficits and outcome after aneurysmal subarachnoid hemorrhage.METHODS:One hundred adult patients with aneurismal SAH were prospectively evaluated. Besides the baseline characteristics, daily C-reactive protein levels were prospectively measured until day 10 after subarachnoid hemorrhage. The primary end point was outcome assessed by Glasgow Outcome Scale, the secondary was the occurrence of delayed ischemic neurological deficits (DINDs).RESULTS:A progressive increase in the CRP levels from the admission to 3rd postictal day was observed, followed by a slow decrease until the 9th day. Hemodynamic changes in TCD were associated with higher serum CRP levels. Patients with lower GCS scores presented with increased CRP levels. Patients with higher Hunt and Hess grades on admission developed significantly higher CRP serum levels. Patients with higher admission Fisher grades showed increased levels of CRP. A statistically significant inverse correlation was established in our series between CRP serum levels and GOS on discharge and CRP levels.CONCLUSIONS:Higher C-reactive protein serum levels are associated with worse clinical outcome and the occurrence of delayed ischemic neurological deficits. Because C-reactive protein levels were significantly elevated in the early phase, they might be a useful parameter to monitor.

Peginterferon plus ribavirin and sustained virological response rate in HCV-related advanced fibrosis: a real life study

Background: Tolerance and response to antiviral HCV treatment is poor in advanced fibrosis. The aim of this study was to assess SVR rate and its predictive factors in HCV advanced fibrosis patients treated in real life with full dose PEG-IFN plus RBV and to evaluate the adverse events related to treatment. Methods: A multicentric, retrospective study was conducted at six university hospitals. METAVIR F3 and F4 HCV monoinfected patients who were treated with PEG-IFN and RBV had their data analyzed. A stepwise logistic regression analysis was performed to identify the variables independently related to SVR. Adverse events were recorded during treatment. Results: 308 patients were included, 75% genotype 1 and 23% genotype 3. METAVIR F3 was present in 39% and F4 in 61% of patients. The median Child Pugh score for F4 patients was 5 (5–9). The global SVR rate was 34%, 11% were relapsers and 55% were nonresponders. SVR rates were similar between patients treated with PEG-IFN alfa 2a or alfa 2b (p = 0.24). SVR rates according to Child–Pugh score were 26% (Child A) and 18% (Child B). The independent factors related to SVR in F4 patients were genotype 3, RVR and fewer Child Pugh score points. Treatment interruption occurred in 31% patients and death occurred in 1.9%, all with liver cirrhosis. Conclusion: Treatment of HCV in patients with advanced fibrosis should not be postponed. However, a very careful evaluation of cirrhotic patients must be performed before treatment is indicated and careful monitoring is required during treatment.

Effects of substrate temperature, substrate orientation, and energetic atomic collisions on the structure of GaN films grown by reactive sputtering

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Prevention of rat liver fibrosis and carcinogenesis by coffee and caffeine

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)