Papers by Silvia Cangussu

Scientific reports, Mar 21, 2018
Smokers, who generally present with lung damage, are more anxious than non-smokers and have an as... more Smokers, who generally present with lung damage, are more anxious than non-smokers and have an associated augmented risk of panic. Considering that lung damage signals specific neural pathways that are related to affective responses, the aim of the present study was to evaluate the influence of pulmonary injury on anxiety and panic-like behaviours in animals exposed to cigarette smoke with and without tobacco. Male Wistar rats were divided into the following groups: a control group (CG); a regular cigarette group (RC); and a tobacco-free cigarette (TFC) group. Animals were exposed to twelve cigarettes per day for eight consecutive days. The animals were then exposed to an elevated T-maze and an open field. The RC and TFC groups presented increases in inflammatory cell inflow, antioxidant enzyme activity, and TBARS levels, and a decrease in the GSH/GSSG ratio was observed in the TFC group. Exposure to RC smoke reduced anxiety and panic-related behaviours. On the other hand, TFC induc...
"Critérios não suficientemente claros, além de abusos por parte de alguns pesqui... more "Critérios não suficientemente claros, além de abusos por parte de alguns pesquisadores, distorcem autoria de publicações, com prejuízos que vêm sendo sistematicamente desconsiderados"

Analytical Methods, 2013
ABSTRACT In this work efficient methods to determine copper and iron in dog serum samples by grap... more ABSTRACT In this work efficient methods to determine copper and iron in dog serum samples by graphite furnace atomic absorption spectrometry were developed. The samples were diluted at a 1:9 or 1:19 (for Cu and Fe, respectively) ratio with 1% (v/v) nitric acid containing a 0.1% Triton X-100 solution. Rhodium for copper and no modifier for iron proved to be the better permanent modifier. Optimization included fractional factorial planning using Pareto and the CCD designs. For both analytes the working linear range was 0–100 mg L−1 (r2 > 0.99). The obtained LOQ was 19.3 ± 2.8 μg L−1 for Cu and 16.5 ± 0.2 μg L−1 for Fe. Aqueous and matrix matching calibration curves had average angular coefficients that were not statistically different, i.e. the matrix effect was absent for both analytes. The accuracy was checked by recovery tests with an average of 101 ± 4% (n = 45) for Cu and 90 ± 3% for Fe (n = 45). The certified reference material Seronorm™ Trace Elements Serum L-1 obtained was 1705 ± 20 μg L−1 for Cu (certified: 1691 ± 84 μg L−1) and 1.40 ± 1.22 mg L−1 for Fe (certified: 1.43 ± 0.08 mg L−1). Cu and Fe levels in 39 canine serum samples – 9 uninfected, 19 symptomatic and 11 asymptomatic dogs naturally infected with Leishmania chagasi – ranged from 374 to 913 μg L−1, and 1103 to 4260 μg L−1, respectively. Cu was higher in symptomatic than in asymptomatic and control dogs, and Fe was significantly lower in symptomatic than in either asymptomatic or control dogs.

International Journal of Experimental Pathology, 2014
Canine visceral leishmaniasis (CVL) is a severe and fatal systemic chronic inflammatory disease. ... more Canine visceral leishmaniasis (CVL) is a severe and fatal systemic chronic inflammatory disease. We investigated the alterations in, and potential associations among, antioxidant enzymes, trace elements and histopathology in CVL. Blood and tissue levels of Cu-Zn superoxide dismutase, catalase and glutathione peroxidase were measured in mixed-breed dogs naturally infected with Leishmania infantum chagasi, symptomatic (n = 19) and asymptomatic (n = 11). Serum levels of copper, iron, zinc, selenium and nitric oxide, and plasma lipid peroxidation were measured. Histological and morphometric analyses were conducted of lesions in liver, spleen and lymph nodes. We found lower blood catalase and glutathione peroxidase activity to be correlated with lower iron and selenium respectively. However, higher activity of Cu-Zn superoxide dismutase was not correlated with the increase in copper and decreased in zinc observed in infected animals compared to controls. Organ tissue was characterized by lower enzyme activity in infected dogs than in controls, but this was not correlated with trace elements. Lipid peroxidation was higher in symptomatic than in asymptomatic and control dogs and was associated with lesions such as chronic inflammatory reaction, congestion, haemosiderin and fibrosis. Systemic iron deposition was observed primarily in the symptomatic dogs showing a higher tissue parasite load. Dogs with symptomatic CVL displayed enhanced LPO and Fe tissue deposition associated with decreased levels of antioxidant enzymes. These results showed new points in the pathology of CVL and might open new treatment perspectives associated with antioxidants and the role of iron in the pathogenesis of CVL. Keywords antioxidant enzymes, canine visceral leishmaniasis, iron, trace elements Canine visceral leishmaniasis (CVL) is a chronic zoonotic disease in Brazil caused by Leishmania (Leishmania) infantum chagasi (syn L. infantum; Mauricio et al. 2000; Shaw 2006) transmitted by the phlebotomine sandfly Lutzomyia longipalpis. Dogs are both natural hosts and the main reservoir of the parasite (Deane & Deane 1955). A typical mononuclear inflammation has been described primarily in organs rich in cells of the mononuclear phagocytic system such as liver, spleen, bone marrow and lymph nodes (Deane & Deane 1955; Alvar et al. 2004). Macrophages generate highly toxic molecules such as reactive oxygen species (ROS) including superoxide radicals (O À 2), hydrogen peroxide (H 2 O 2) and hydroxyl radicals (OH À) and reactive nitrogen species including nitric oxide (NO) to combat Leishmania (
h i g h l i g h t s " Fibres density decrease with the hyperalgesia in Leishmania major infected ... more h i g h l i g h t s " Fibres density decrease with the hyperalgesia in Leishmania major infected C57BL/6 mice. " The pro-inflammatory cytokines upregulate during hyperalgesia in C57BL/6. " The anti-inflammatory cytokines downregulate during hypoalgesia in BALB/c. " Cytokines, innervation and tissue damage are correlated in leishmaniasis.
Revista Brasileira De Entomologia, 2007
Problems regarding the order of authorship of scientific papers have become more frequent and mor... more Problems regarding the order of authorship of scientific papers have become more frequent and more abusive. These problems may have heightened due to the ever increasing pressure to "publish or perish" in the academic world, given that the publication of scientific articles has become the benchmark of success in a field with few job opportunities. This article reviews the abuses in the authorship of scientific papers. Different examples are given of the most common problems and recommendations are provided for authors and journal editors.
Uniform requirements for manuscripts submitted to biomedical journals.

Even though several musicians may have at any one time collaborated on the composition of an oper... more Even though several musicians may have at any one time collaborated on the composition of an opera there exist no records of these works being attributed to more than one author. The same can be said of great literature. For example, William Shakespeare left no works penned with collaborators (Griffith & Babor 2000). In science, abuses related to the authorship of scientific studies occur with the exclusion or the inclusion of non meritorious researchers as authors. During the last few decades, several authors have called attention to problems related to the abuses when determining the authorship of scientific studies (ICMJE 2006). These problems have been steadily rising due to the overestimation of the number of publications an author has (Bennett & Taylor 2003). For example, in the United States most higher learning institutions consider the number of published papers a potential candidate for a faculty position has to be the main criterion for hiring, even when compared to a candidate with a comparatively superior ability to teach (Fleet et al. 2006). This "publish or perish" atmosphere has created a "race to publish" amongst researchers world wide (Brice & Bligh 2004), resulting, many times, in studies of poor quality. In Brazil no similar data are available. Based on our collective experiences within public universities (Instituições Federais de Ensino Superior-IFES), however, the reality in Brazil is not much different from that in many other countries. In fact, the situation has worsened in the last few years due to lack of expansion and reduced renewal of faculty positions in the IFES.

Bioorganic & Medicinal Chemistry
Acetaminophen (APAP) is an antipyretic and analgesic drug that, in high doses, leads to severe li... more Acetaminophen (APAP) is an antipyretic and analgesic drug that, in high doses, leads to severe liver injury and potentially death. Oxidative stress is an important event in APAP overdose. Researchers are looking for natural antioxidants with the potential to mitigate the harmful effects of reactive oxygen species in different models. Lycopene has been widely studied for its antioxidant properties. The aim of this study was to evaluate the antioxidant potential of lycopene pretreatment in APAP-induced liver injury in C57BL/6 mice. C57BL/6 male mice were divided into the following groups: control (C); sunflower oil (CO); acetaminophen 500mg/kg (APAP); acetaminophen 500mg/kg+lycopene 10mg/kg (APAP+L10), and acetaminophen 500mg/kg+lycopene 100mg/kg (APAP+L100). Mice were pretreated with lycopene for 14 consecutive days prior to APAP overdose. Analyses of blood serum and livers were performed. Lycopene was able to improve redox imbalance, decrease thiobarbituric acid reactive species level, and increase CAT and GSH levels. In addition, it decreased the IL-1β expression and the activity of MMP-2. This study revealed that preventive lycopene consumption in C57BL/6 mice can attenuate the effects of APAP-induced liver injury. Furthermore, by improving the redox state, and thus indicating its potential antioxidant effect, lycopene was also shown to have an influence on inflammatory events.
Journal of Ethnopharmacology

Oxidative medicine and cellular longevity, 2018
This study aims to evaluate the effects of a high-fat diet and mechanical ventilation on the pulm... more This study aims to evaluate the effects of a high-fat diet and mechanical ventilation on the pulmonary and systemic inflammatory response in C57BL/6 mice. Male C57BL/6 mice were divided into two groups: one received a standard diet, and the other received a high-fat diet. After 10 weeks, the groups were further divided into two groups each: control group (CG), mechanical ventilation group (MVG), diet group (DG), and diet mechanical ventilation group (DMVG). MVG and DMVG underwent mechanical ventilation for 60 minutes. All animals were euthanized for subsequent analysis. Animals receiving a high-fat diet presented higher body mass, adipose index, and greater adipocyte area. In the lung, the expression of HMGB1 was greater in DG and DMVG than in CG and MVG. CCL2 and IL-22 levels in MVG and DMVG were increased compared to those in CG and DG, whereas IL-10 and IL-17 were decreased. Superoxide dismutase activity was higher in MVG and DMVG than in CG. Catalase activity was lower in DG tha...

Shock (Augusta, Ga.), Jan 30, 2017
Mechanical ventilation (MV) may induce or aggravate lung injury through the production of cytokin... more Mechanical ventilation (MV) may induce or aggravate lung injury through the production of cytokines, inflammatory infiltration of neutrophils, and changes in the permeability of the alveolar-capillary barrier. The use of positive end-expiratory pressure (PEEP) helps improve gas exchanges avoiding alveolar collapse at the end of expiration. The present study aimed to analyze inflammatory response and redox imbalance in lungs of rats submitted to MV with and without PEEP. Eighteen Wistar rats were divided into three groups: control (CG), PEEP group (PG), and zero PEEP (ZEEP) group (ZG). PG and ZG were submitted to MV for 60 min with or without PEEP, respectively. Subsequently, the animals were euthanized, and blood, bronchoalveolar lavage fluid, and lungs were collected for analyses. The number of neutrophils was higher in PG compared with CG. Leucocyte and neutrophil influx in bronchoalveolar lavage fluid was higher in PG compared with CG. PG showed an increase in alveolar area compa...

International immunopharmacology, Jan 22, 2017
The alveolar surfactant, which composition consists of a unique and complex mixture of lipids and... more The alveolar surfactant, which composition consists of a unique and complex mixture of lipids and proteins, has immunomodulatory action. This study aimed to evaluate the effects of exogenous surfactant on pulmonary inflammatory response in mice exposed to cigarette smoke (CS). Twenty-four mice C57BL/6 were divided into four groups: control group exposed to ambient air (CG); surfactant treated group (SG); CS exposed group (CSG) and CS exposed group treated with surfactant (CSSG). For five days, CSG and CSSG were exposed to 12 commercial cigarettes/day and SG and CSSG received the surfactant by intranasal instillation. At the end of the experiment, the animals were euthanatized for the collection of bronchoalveolar lavage fluid (BALF) and lungs. The total number of leukocytes in BALF increased in CSG compared to CG, however, there was a decrease in CSSG compared to CSG. There was an increase in lipid peroxidation in SG and CSG compared to CG while there was a decrease in CSSG compared...

Bioorganic & medicinal chemistry, Feb 18, 2016
Acetaminophen (APAP) is an antipyretic and analgesic drug that, in high doses, leads to severe li... more Acetaminophen (APAP) is an antipyretic and analgesic drug that, in high doses, leads to severe liver injury and potentially death. Oxidative stress is an important event in APAP overdose. Researchers are looking for natural antioxidants with the potential to mitigate the harmful effects of reactive oxygen species in different models. Lycopene has been widely studied for its antioxidant properties. The aim of this study was to evaluate the antioxidant potential of lycopene pretreatment in APAP-induced liver injury in C57BL/6 mice. C57BL/6 male mice were divided into the following groups: control (C); sunflower oil (CO); acetaminophen 500mg/kg (APAP); acetaminophen 500mg/kg+lycopene 10mg/kg (APAP+L10), and acetaminophen 500mg/kg+lycopene 100mg/kg (APAP+L100). Mice were pretreated with lycopene for 14 consecutive days prior to APAP overdose. Analyses of blood serum and livers were performed. Lycopene was able to improve redox imbalance, decrease thiobarbituric acid reactive species lev...

PLOS ONE, 2016
We developed a novel murine model of long-term infection with Trypanosoma cruzi with the aim to e... more We developed a novel murine model of long-term infection with Trypanosoma cruzi with the aim to elucidate the pathogenesis of megacolon and the associated adaptive and neuromuscular intestinal disorders. Our intent was to produce a chronic stage of the disease since the early treatment should avoid 100% mortality of untreated animals at acute phase. Treatment allowed animals to be kept infected and alive in order to develop the chronic phase of infection with low parasitism as in human disease. A group of Swiss mice was infected with the Y strain of T. cruzi. At the 11 th day after infection, a subgroup was euthanized (acute-phase group) and another subgroup was treated with benznidazole and euthanized 15 months after infection (chronic-phase group). Whole colon samples were harvested and used for studying the histopathology of the intestinal smooth muscle and the plasticity of the enteric nerves. In the acute phase, all animals presented inflammatory lesions associated with intense and diffuse parasitism of the muscular and submucosa layers, which were enlarged when compared with the controls. The occurrence of intense degenerative inflammatory changes and increased reticular fibers suggests inflammatoryinduced necrosis of muscle cells. In the chronic phase, parasitism was insignificant; however, the architecture of Aüerbach plexuses was focally affected in the inflamed areas, and a significant decrease in the number of neurons and in the density of intramuscular nerve bundles was detected. Other changes observed included increased thickness of the colon wall, diffuse muscle cell hypertrophy, and increased collagen deposition, indicating early fibrosis in the damaged areas. Mast cell count significantly increased in the muscular layers. We propose a model for studying the long-term (15 months) pathogenesis of Chagasic PLOS ONE |

Cell Biology International Reports, 2012
Neural precursor differentiation from mouse ES (embryonic stem) cells have been demonstrated usin... more Neural precursor differentiation from mouse ES (embryonic stem) cells have been demonstrated using EB (embryoid body), co-culture on stromal feeder layers, and in the absence of external inducing signals. Most of available mouse ES cell original research articles have worked with only six different cell lines. Our goals were to isolate one new mouse ES lineage, and perform a detailed immunocytochemistry study during neural differentiation, making use of an EB strategy protocol following the generation of neural progenitors, glial cells and postmitotic neurons. The dynamics of differentiation of ES cell derived neuronal precursors into differentiated glia cells and neurons were followed in vitro and correlated to exposure to specific elements of feeder medium. Morphological aspects of generated cellular types, including its immunocytochemical expression of differentiation markers were studied. Immuno-positivity against b-III tubulin, PGP and TH (tyrosine hydroxylase) was observed from stage I. Approximately 80% of cells were positive for TH at stage I. The first glial cell type appears in stage III. TH, PGP or b-III tubulin-positive cells with neuronal typical morphology only being seen in stage III when TH-positive cells corresponded to approximately 12% of total cells. Variations among other literature findings can be explained by the choice we made to use a newly isolated ES cell line. As colonies may behave differently during neuronal differentiation, it reinforces the necessity of studying original ES cell lines.

Recent in vitro and in vivo studies on anthocyanins confirmed numerous health-promoting effects i... more Recent in vitro and in vivo studies on anthocyanins confirmed numerous health-promoting effects in humans. Daily anthocyanin intake can be estimated via food databases, but the amount absorbed by the organism still remains uncertain because anthocyanin bioavailability is yet to be elucidated in its entirety. For this purpose, suitable and validated methods of sample preparation and analysis are required. Therefore, a sample preparation method for anthocyanin metabolite analysis in plasma was successfully established and validated. The validation yielded acceptable results for the anthocyanins in terms of recovery (54-108%) and precision (coefficient of variation (CV) < 15%). The UHPLC-MS method used in the consecutive reaction monitoring (CRM) mode was sufficiently sensitive, resulting in limits of detection <2.3 ng/mL and limits of quantification < 8.1 ng/mL with associated repeatability of the MS system with CVs of <5.1%. In addition, a method for the sum parameter determination of anthocyanidins in urine comprising solely the evaporation of acidified samples was developed, validated, and successfully applied to real samples. The results showed that this method is applicable for the methylated anthocyanidins, but not for the hydroxylated anthocyanidins, due to the chosen CRM modes required for optimum selectivity.
Experimental Parasitology, Nov 30, 2012
h i g h l i g h t s " Fibres density decrease with the hyperalgesia in Leishmania major infected ... more h i g h l i g h t s " Fibres density decrease with the hyperalgesia in Leishmania major infected C57BL/6 mice. " The pro-inflammatory cytokines upregulate during hyperalgesia in C57BL/6. " The anti-inflammatory cytokines downregulate during hypoalgesia in BALB/c. " Cytokines, innervation and tissue damage are correlated in leishmaniasis.

Regulatory toxicology and pharmacology : RTP, Jan 17, 2018
Taurine is the major free amino acid found in mammalian cells and is known to be an antioxidant a... more Taurine is the major free amino acid found in mammalian cells and is known to be an antioxidant and membrane-stabilizing agent. This study aimed to evaluate the effects of taurine on oxidative stress and inflammatory response in the lungs of mice exposed to cigarette smoke. Fifty male C57BL/6 mice were divided into 5 groups: control group (CG), vehicle group (VG), taurine group (TG), cigarette smoke group (CSG), and cigarette smoke + taurine group (CSTG). For five consecutive days, CSG and CSTG were exposed to 4 cigarettes 3 times a day. Taurine administration was able to reduce total leukocytes in bronchoalveolar lavage fluid in CSTG compared to CSG. There was an increase in antioxidant superoxide dismutase and catalase activity in CSG compared to that in CG and TG, and a decrease in CSTG compared to CSG. There was an increase in the concentration of TNF and IL-17 in CSG and CSTG compared to CG and TG. There was an increase in the concentration of IL-22 in CSG compared to CG and TG...

International Journal of Chronic Obstructive Pulmonary Disease, 2016
This study aimed to evaluate the effects of a high refined carbohydrate diet and pulmonary inflam... more This study aimed to evaluate the effects of a high refined carbohydrate diet and pulmonary inflammatory response in C57BL/6 mice exposed to cigarette smoke (CS). Twentyfour male mice were divided into four groups: control group (CG), which received a standard diet; cigarette smoke group (CSG), which was exposed to CS; a high refined carbohydrate diet group (RG), which received a high refined carbohydrate diet; and a high refined carbohydrates diet and cigarette smoke group (RCSG), which received a high refined carbohydrate diet and was exposed to CS. The animals were monitored for food intake and body weight gain for 12 weeks. After this period, the CSG and RCSG were exposed to CS for five consecutive days. At the end of the experimental protocol, all animals were euthanized for subsequent analyses. There was an increase of inflammatory cells in the bronchoalveolar lavage fluid (BALF) of CSG compared to CG and RCSG compared to CG, CSG, and RG. In addition, in the BALF, there was an increase of tumor necrosis factor alpha in RCSG compared to CG, CSG, and RG; interferon gamma increase in RCSG compared to the CSG; and increase in interleukin-10 in RCSG compared to CG and RG. Lipid peroxidation increased in RCSG compared to CG, CSG, and RG. Furthermore, the oxidation of proteins increased in CSG compared to CG. The analysis of oxidative stress showed an increase in superoxide dismutase in RCSG compared to CG, CSG, and RG and an increase in the catalase activity in RCSG compared with CG. In addition, there was a decrease in the glutathione reduced/glutathione total ratio of CSG, RG, and RCSG compared to CG. Therefore, the administration of a high refined carbohydrate diet promoted an increase in pulmonary inflammation and oxidative stress in mice exposed to CS.
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Papers by Silvia Cangussu