Christiane Teixeira Cartelle - Academia.edu (original) (raw)
Papers by Christiane Teixeira Cartelle
Introducao: A proliferacao celular estimulada por H. pylori pode ter papel significativo na carci... more Introducao: A proliferacao celular estimulada por H. pylori pode ter papel significativo na carcinogenese gastrica. Admite-se que a infeccao na infância determine o risco de desenvolvimento do câncer gastrico. O microrganismo e capaz de modificar o turnover epitelial da mucosa gastrica induzindo hiperproliferacao e apoptose. O aumento daproliferacao pode ocorrer diretamente pela acao de fatores ligados a bacteria, indiretamente pela resposta inflamatoria do hospedeiro ou pela interacao entre ambos. Entre os fatores relacionados a bacteria destaca-se a infeccao por amostras cagA positivas que induzem a taxas maiores de proliferacao celular. Muitos estudos sobre proliferacao celular tem sido realizados com foco em adultos. Os estudos em criancas sao escassos e nao abordam as diferencas em relacao ao status cagA e doencas associadas a infeccao. Objetivos: Analisar a proliferacao epitelial gastrica em criancas infectadas por H. pylori em relacao com o tipo de amostra, associacao com ulc...
<p>(A and B) The chronic-phase infected group presented increased thickness of the total co... more <p>(A and B) The chronic-phase infected group presented increased thickness of the total colon wall compared with the acute-phase infected group and with the control group. Values represent means ± SEM. *p = 0.001, **p = 0.026. N = 10 for each experimental and control group. The results represent two independent experiments. Black: infected groups; white: control groups.</p
<p>A, C, E, G, and H represent acute-phase aspects (11 d.a.i.). B, D, F, and I represent ch... more <p>A, C, E, G, and H represent acute-phase aspects (11 d.a.i.). B, D, F, and I represent chronic-phase aspects (15 m.a.i.). (A) The colons of the control group of paired animals in the acute phase present normal cellularity and thickness. (B) In the chronic phase, no alterations were observed in the control group. (C) In acute-phase infected animals, a mononuclear inflammatory infiltrate was observed in the submucosal and muscular layers (arrow). In the myenteric plexus (arrowhead) and in the inner muscular layer, there is evidence of muscle fiber necrosis (thick arrow). This transmural pattern is merged with non-inflamed areas (not shown). (D) In contrast, in the chronic-phase infected group, mononuclear infiltrates are focal and more intense in the outer muscular layer in the periganglionar and perivascular areas (arrow). (E) Intense parasitism (inset,arrow) is associated with inflammatory infiltrates in the acute phase. (F) In the chronic phase, parasites are scarce and not associated with inflammatory foci (inset). (G) The acute-phase infected group showed strong iNOS positivity associated with inflammatory and degenerative changes in the myenteric plexus (arrowheads) compared (I) with the weak staining in inflammatory cells (arrow, and inset) in the chronic-phase infected group. A possible glial cell of ganglia (arrowhead) is also stained. (H) In addition, a greater amount of reticular fibers with thickened areas around the ganglia (arrow) were present in the acute phase. The results represent two independent experiments. A, B, C, D, I, H Magnification at 20x. Scale bar corresponds to 20 μm. E, F Magnification at 4x. Scale Bar corresponds to 100 μm. G Magnification at 40x. Scale bar corresponds to 10 μm. HE staining in A, B, C and D. Immunohistochemistry with anti-<i>T</i>. <i>cruzi</i> antibody in E, and F, and insets of E and F. Immunohistochemistry with anti-iNOS antibody in G and I. Silver Gomori staining in H.</p
A infeccao cronica da mucosa gastrica por H. pylori e a principal causa da gastrite cronica (GC) ... more A infeccao cronica da mucosa gastrica por H. pylori e a principal causa da gastrite cronica (GC) implicado na patogenese da atrofia e da metaplasia intestinal (MI), condicoes de risco para o desenvolvimento do carcinoma gastrico (CaG). A infeccao na infância determina risco de desenvolvimento do câncer gastrico justificando estudos comparados entre criancas e adultos. O microrganismo modifica o turnover da mucosa gastrica induzindo hiperproliferacao e apoptose. No entanto, os mecanismos e vias operantes nos processos proliferativos e apoptoticos nao sao bem entendidos. Apesar de estudos mostrarem relacao entre carcinogenese gastrica e expressao da sintase de oxido nitrico induzida (iNOS), ainda nao se sabe qual a correlacao entre inflamacao, apoptose e ativacao desta enzima nas condicoes de risco para transformacao maligna associadas a infeccao pelo H. pylori. Neste trabalho investigamos as vias apoptoticas nas gastrites, na mucosa gastrica de criancas e adultos e correlacionamos a ...
Beneficial Microbes, 2019
This study evaluated the effects of Bifidobacterium longum 51A on the intestinal mucosa and infla... more This study evaluated the effects of Bifidobacterium longum 51A on the intestinal mucosa and inflammatory response in experimental colitis. Colitis was induced by administration of 3.5% dextran sodium sulphate (DSS) solution for 7 days. Two periods of administration were performed: treatment (T) group, mice received Bifidobacterium only during disease induction (7 days); total treatment (TT) group, mice received Bifidobacterium for 10 days before and during disease induction. The probiotic effects on intestinal permeability, inflammatory infiltrate, histological analysis, cytokines, chemokines and sIgA were evaluated. Bifidobacterium administration in the T group showed reduction in intestinal permeability and lower IL-1β, myeloperoxidase, and eosinophil peroxidase levels compared to those in the colitis group (P<0.05). Bifidobacterium administration in the TT group attenuated severe lesions in the colon and reduced eosinophil peroxidase level (P<0.05). B. longum 51A treatment ...
Neuroscience Letters, 2019
Two billion people are chronically infected with Toxoplasma gondii worldwide with unknown consequ... more Two billion people are chronically infected with Toxoplasma gondii worldwide with unknown consequences. Important neurological diseases have been associated to the brain infection, making essential to understand the neurophysiological changes associated with the neuronal encystment. T. gondii may subvert neuronal functions modifying neurotransmitter concentration in chronically infected mice but the molecular mechanisms involved are still unclear. Parasites were observed inside neuronal cells in cultures from 24-192 hs. The rate of infection increased with time. Neurite density decreased affecting network functionality. Neuronal survival was affected and we detected the presence of cysts inside neuronal bodies and dilated portions of neurites in association with a relative increase of TH-positive neuritic area without noticeable changes in DA immunofluorescence pattern. These results advance our knowledge of the interaction between T. gondii and the neuronal network of the host.
Intensive Care Medicine Experimental, 2019
Background: In addition to the risk of developing ventilator-induced lung injury, patients with A... more Background: In addition to the risk of developing ventilator-induced lung injury, patients with ARDS are at risk of developing hyperoxic injury due the supra-physiological oxygen supplementation clinically required to reverse hypoxemia. Alterations of endogenous surfactant system participate in the pulmonary dysfunction observed in ARDS. Administration of exogenous surfactant could have protective effects during hyperoxia. Methods: Male BALB/c mice (8-10 weeks), a strain highly sensitive to hyperoxia, received the exogenous surfactant-containing protein SP-B and SP-C by intranasal instillation 12 h before starting 24 h of exposure to hyperoxia in an inhalation chamber and were compared to mice receiving hyperoxia alone and to controls subjected to normoxia. Results: Compared to the hyperoxia group, the administration of exogenous surfactant was able to reduce lung inflammation through a reduction in the influx of neutrophils and inflammatory biomarkers such as TNF, IL-17, and HMGB1 expression. The antioxidant activity prevented oxidative damage by reducing lipid peroxidation and protein carbonylation and increasing superoxide dismutase activity when compared to the hyperoxia group. Conclusion: Our results offer new perspectives on the effects and the mechanism of exogenous surfactant in protecting the airway and lungs, in oxygen-rich lung microenvironment, against oxidative damage and aggravation of acute inflammation induced by hyperoxia.
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...
International Journal of Experimental Pathology, 2017
Toxoplasmosis represents one of the most common zoonoses worldwide. Its agent, Toxoplasma gondii,... more Toxoplasmosis represents one of the most common zoonoses worldwide. Its agent, Toxoplasma gondii, causes a severe innate pro-inflammatory response. The indigenous intestinal microbiota promotes host animal homoeostasis and may protect the host against pathogens. Germ-free (GF) animals provide an important tool for the study of interactions between host and microbiota. In this study, we assessed the role of indigenous microorganisms in disease development utilizing a murine toxoplasmosis model, which includes conventional (CV) and GF NIH Swiss mice. CV and GF mice orally inoculated with T. gondii had similar survival curves. However, disease developed differently in the two animal groups. In CV mice, intestinal permeability increased and levels of intestinal pro-inflammatory cytokines were altered. In GF animals, there were discrete epithelial degenerative changes and mucosal oedema, but the liver and lungs displayed significant lesions. We conclude that, despite similar survival curves, CV animals succumb to an exaggerated inflammatory response, whereas GF mice fail to produce an adequate systemic response.
Journal of Neuroinfectious Diseases, 2016
Chagas disease is a chronic disorder caused by the Trypanosoma cruzi protozoan. The infection cau... more Chagas disease is a chronic disorder caused by the Trypanosoma cruzi protozoan. The infection causes alterations to the enteric nervous system such as megaesophagus and megacolon. There is evidence of denervation of myenteric ganglia. The intense parasitism of acute phase affects neuronal integrity but contrasts with the absence of parasites and the discreet inflammatory process of chronic phase, indicating a progressive injury mechanism that needs to be better understood in the megacolons. The potential selectivity of enteric neurons classes affected by the progression of the disease is not yet clear. Nitrergic neurons which co-localize other neurotransmitters represent the most common inhibitory neuron of the ENS. Recently a chronic stage of the Chagas disease was reproduced experimentally in a suitable murine model of megacolon. Considering the limitation of studying human intestine and the controversy on the pattern of nNOS involvement in chagasic megacolon, we decided to assess the nitrergic neurons in the myenteric plexus of mice. We used antibodies against structural protein gene product 9.5 (PGP 9.5) and functional neuronal nitric oxide synthase (n-NOS) at the acute and chronic phase of the disease to quantify myenteric ganglionar neurons in the colon of infected and non-infected mice. We found a reduction in the ganglionar number of neurons detected by anti-protein gene product 9.5 antibodies in colon from mice at the chronic stage. However, the number of nitrergic neurons per ganglia remained unchanged along the acute to phase chronic of the disease. Our findings indicate a long-term preservation of nitregic neurons detrimental to other classes of enteric in our model of experimental Chagas disease. We propose that differential loss of enteric neurons is at least one of the structural substrate for the development of the longterm morphfunctional changes that lead to the megacolon.
Beneficial Microbes, 2016
Indigenous microbiota plays a crucial role in the development of several intestinal diseases, inc... more Indigenous microbiota plays a crucial role in the development of several intestinal diseases, including mucositis. Gastrointestinal mucositis is a major and serious side effect of cancer therapy, and there is no effective therapy for this clinical condition. However, some probiotics have been shown to attenuate such conditions. To evaluate the effects of Saccharomyces cerevisiae UFMG A-905 (Sc-905), a potential probiotic yeast, we investigated whether pre- or post-treatment with viable or inactivated Sc-905 could prevent weight loss and intestinal lesions, and maintain integrity of the mucosal barrier in a mucositis model induced by irinotecan in mice. Only post-treatment with viable Sc-905 was able to protect mice against the damage caused by chemotherapy, reducing the weight loss, increase of intestinal permeability and jejunal lesions (villous shortening). Besides, this treatment reduced oxidative stress, prevented the decrease of goblet cells and stimulated the replication of ce...
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 |
International Journal of Infectious Diseases, 2016
Objectives: Different methods for the classification of leprosy have been proposed since the 1930... more Objectives: Different methods for the classification of leprosy have been proposed since the 1930s. The aim of this study was to compare the current methods at a referral center in Brazil. Methods: The World Health Organization (WHO) operational classification was compared to the Ridley and Jopling classification, the Madrid classification, and a classification based on the number of body areas affected by skin and/or neural lesions (NBAA). The correlation between the clinical and histopathological components of the Ridley and Jopling classification was assessed. Results: The agreement between the WHO operational classification and the Ridley and Jopling classification was 77.6% (kappa = 0.53). The WHO operational classification tended to overestimate the number of multibacillary patients. The WHO operational classification showed its best agreement with the NBAA. There was perfect agreement between the clinical and histopathological Ridley and Jopling classification in 46.9% of the patients. Conclusions: The agreement between the WHO operational classification and the Ridley and Jopling classification was better than any other purely clinical classification, reinforcing the importance and simplicity of the operational method. Although major disagreement between the clinical and histopathological Ridley and Jopling classification was uncommon, perfect agreement occurred in less than half of the cases, and was even lower for the borderline lepromatous and tuberculoid forms. Possible reasons for the differences are discussed; these showed that there may be room for improvement in the Ridley and Jopling classification histopathological criteria.
Microbiology (Reading, England), Jan 28, 2015
Mucositis is one of the most debilitating side effects of chemotherapy and some previous studies ... more Mucositis is one of the most debilitating side effects of chemotherapy and some previous studies suggest a role for indigenous microbiota in the course of this pathology. Therefore, the aim of our study was to evaluate the differences in phenotype between germ-free (GF) and conventional (CV) mice, and the role of β-glucuronidase-producing bacteria in the development of irinotecan treatment in a murine model. After mucositis induction, CV mice showed a significant increase in all inflammatory parameters when compared to GF mice. CV animals also showed more lesions of intestinal epithelium, coherent with their higher intestinal permeability. The conventionalization of GF animals reversed their phenotype to that found in CV mice. In addition, gnotobiotic mice monoassociated with an Escherichia coli strain producing β-glucuronidase showed an increased permeability when compared to gnotobiotic mice monoassociated with an E. coli strain deleted for the gene encoding β-glucuronidase, but t...
European Journal of Immunology, 2014
During oral infection, mucosal immunity assumes a predominant role. Here, we addressed the role o... more During oral infection, mucosal immunity assumes a predominant role. Here, we addressed the role of mast cells (MCs), which are mainly located in mucosa during oral infection with Toxoplasma gondii, using MC-deficient (W/W v) mice. We show that in the absence of MCs the resistance of W/W v mice to oral infection was considerably reduced. W/W v mice uniformly succumbed within 15 days of infection after administration of cysts of the ME49 strain of T. gondii. The rapid lethality of T. gondii in W/W v mice correlated with a delayed Th1-cell response, since IFN-γ and IL-12 levels peaked in the later phase of the infection. In vitro, BM-derived MCs were able to recognize parasite lysate in a MyD88-dependent way, reaffirming the role of this TLR adapter in immune responses to T. gondii. The importance of MCs in vivo was confirmed when W/W v mice reconstituted with BM-derived MCs from control mice retrieved an early strong Th1-cell response and specially a significant IL-12 production. In conclusion, MCs play an important role for the development of a protective immune response during oral infection with T. gondii.
Journal of Neuroinflammation, 2014
Background Herpes simplex 1 (HSV-1) causes various human clinical manifestations, ranging from si... more Background Herpes simplex 1 (HSV-1) causes various human clinical manifestations, ranging from simple cold sores to encephalitis. Innate immune cells recognize pathogens through Toll-like receptors (TLRs), thus initiating the immune response. Previously, we demonstrated that the immune response against HSV-1 is dependent on TLR2 and TLR9 expression and on IFN gamma production in the trigeminal ganglia (TG) of infected mice. In this work, we further investigated the cells, molecules, and mechanisms of HSV-1 infection control, especially those that are TLR-dependent. Methods C57BL/6 wild-type (WT), TLR2−/−, TLR9−/−, and TLR2/9−/− mice were intranasally infected with HSV-1. On the viral peak day, the TG and brains were collected from mice and TLR expression was measured in the TG and brain and inducible nitric oxide synthase (iNOS) expression was measured in the TG by real-time PCR. Immunofluorescence assays were performed in mice TG to detect iNOS production by F4/80+ cells. Intraperi...
Introducao: A proliferacao celular estimulada por H. pylori pode ter papel significativo na carci... more Introducao: A proliferacao celular estimulada por H. pylori pode ter papel significativo na carcinogenese gastrica. Admite-se que a infeccao na infância determine o risco de desenvolvimento do câncer gastrico. O microrganismo e capaz de modificar o turnover epitelial da mucosa gastrica induzindo hiperproliferacao e apoptose. O aumento daproliferacao pode ocorrer diretamente pela acao de fatores ligados a bacteria, indiretamente pela resposta inflamatoria do hospedeiro ou pela interacao entre ambos. Entre os fatores relacionados a bacteria destaca-se a infeccao por amostras cagA positivas que induzem a taxas maiores de proliferacao celular. Muitos estudos sobre proliferacao celular tem sido realizados com foco em adultos. Os estudos em criancas sao escassos e nao abordam as diferencas em relacao ao status cagA e doencas associadas a infeccao. Objetivos: Analisar a proliferacao epitelial gastrica em criancas infectadas por H. pylori em relacao com o tipo de amostra, associacao com ulc...
<p>(A and B) The chronic-phase infected group presented increased thickness of the total co... more <p>(A and B) The chronic-phase infected group presented increased thickness of the total colon wall compared with the acute-phase infected group and with the control group. Values represent means ± SEM. *p = 0.001, **p = 0.026. N = 10 for each experimental and control group. The results represent two independent experiments. Black: infected groups; white: control groups.</p
<p>A, C, E, G, and H represent acute-phase aspects (11 d.a.i.). B, D, F, and I represent ch... more <p>A, C, E, G, and H represent acute-phase aspects (11 d.a.i.). B, D, F, and I represent chronic-phase aspects (15 m.a.i.). (A) The colons of the control group of paired animals in the acute phase present normal cellularity and thickness. (B) In the chronic phase, no alterations were observed in the control group. (C) In acute-phase infected animals, a mononuclear inflammatory infiltrate was observed in the submucosal and muscular layers (arrow). In the myenteric plexus (arrowhead) and in the inner muscular layer, there is evidence of muscle fiber necrosis (thick arrow). This transmural pattern is merged with non-inflamed areas (not shown). (D) In contrast, in the chronic-phase infected group, mononuclear infiltrates are focal and more intense in the outer muscular layer in the periganglionar and perivascular areas (arrow). (E) Intense parasitism (inset,arrow) is associated with inflammatory infiltrates in the acute phase. (F) In the chronic phase, parasites are scarce and not associated with inflammatory foci (inset). (G) The acute-phase infected group showed strong iNOS positivity associated with inflammatory and degenerative changes in the myenteric plexus (arrowheads) compared (I) with the weak staining in inflammatory cells (arrow, and inset) in the chronic-phase infected group. A possible glial cell of ganglia (arrowhead) is also stained. (H) In addition, a greater amount of reticular fibers with thickened areas around the ganglia (arrow) were present in the acute phase. The results represent two independent experiments. A, B, C, D, I, H Magnification at 20x. Scale bar corresponds to 20 μm. E, F Magnification at 4x. Scale Bar corresponds to 100 μm. G Magnification at 40x. Scale bar corresponds to 10 μm. HE staining in A, B, C and D. Immunohistochemistry with anti-<i>T</i>. <i>cruzi</i> antibody in E, and F, and insets of E and F. Immunohistochemistry with anti-iNOS antibody in G and I. Silver Gomori staining in H.</p
A infeccao cronica da mucosa gastrica por H. pylori e a principal causa da gastrite cronica (GC) ... more A infeccao cronica da mucosa gastrica por H. pylori e a principal causa da gastrite cronica (GC) implicado na patogenese da atrofia e da metaplasia intestinal (MI), condicoes de risco para o desenvolvimento do carcinoma gastrico (CaG). A infeccao na infância determina risco de desenvolvimento do câncer gastrico justificando estudos comparados entre criancas e adultos. O microrganismo modifica o turnover da mucosa gastrica induzindo hiperproliferacao e apoptose. No entanto, os mecanismos e vias operantes nos processos proliferativos e apoptoticos nao sao bem entendidos. Apesar de estudos mostrarem relacao entre carcinogenese gastrica e expressao da sintase de oxido nitrico induzida (iNOS), ainda nao se sabe qual a correlacao entre inflamacao, apoptose e ativacao desta enzima nas condicoes de risco para transformacao maligna associadas a infeccao pelo H. pylori. Neste trabalho investigamos as vias apoptoticas nas gastrites, na mucosa gastrica de criancas e adultos e correlacionamos a ...
Beneficial Microbes, 2019
This study evaluated the effects of Bifidobacterium longum 51A on the intestinal mucosa and infla... more This study evaluated the effects of Bifidobacterium longum 51A on the intestinal mucosa and inflammatory response in experimental colitis. Colitis was induced by administration of 3.5% dextran sodium sulphate (DSS) solution for 7 days. Two periods of administration were performed: treatment (T) group, mice received Bifidobacterium only during disease induction (7 days); total treatment (TT) group, mice received Bifidobacterium for 10 days before and during disease induction. The probiotic effects on intestinal permeability, inflammatory infiltrate, histological analysis, cytokines, chemokines and sIgA were evaluated. Bifidobacterium administration in the T group showed reduction in intestinal permeability and lower IL-1β, myeloperoxidase, and eosinophil peroxidase levels compared to those in the colitis group (P<0.05). Bifidobacterium administration in the TT group attenuated severe lesions in the colon and reduced eosinophil peroxidase level (P<0.05). B. longum 51A treatment ...
Neuroscience Letters, 2019
Two billion people are chronically infected with Toxoplasma gondii worldwide with unknown consequ... more Two billion people are chronically infected with Toxoplasma gondii worldwide with unknown consequences. Important neurological diseases have been associated to the brain infection, making essential to understand the neurophysiological changes associated with the neuronal encystment. T. gondii may subvert neuronal functions modifying neurotransmitter concentration in chronically infected mice but the molecular mechanisms involved are still unclear. Parasites were observed inside neuronal cells in cultures from 24-192 hs. The rate of infection increased with time. Neurite density decreased affecting network functionality. Neuronal survival was affected and we detected the presence of cysts inside neuronal bodies and dilated portions of neurites in association with a relative increase of TH-positive neuritic area without noticeable changes in DA immunofluorescence pattern. These results advance our knowledge of the interaction between T. gondii and the neuronal network of the host.
Intensive Care Medicine Experimental, 2019
Background: In addition to the risk of developing ventilator-induced lung injury, patients with A... more Background: In addition to the risk of developing ventilator-induced lung injury, patients with ARDS are at risk of developing hyperoxic injury due the supra-physiological oxygen supplementation clinically required to reverse hypoxemia. Alterations of endogenous surfactant system participate in the pulmonary dysfunction observed in ARDS. Administration of exogenous surfactant could have protective effects during hyperoxia. Methods: Male BALB/c mice (8-10 weeks), a strain highly sensitive to hyperoxia, received the exogenous surfactant-containing protein SP-B and SP-C by intranasal instillation 12 h before starting 24 h of exposure to hyperoxia in an inhalation chamber and were compared to mice receiving hyperoxia alone and to controls subjected to normoxia. Results: Compared to the hyperoxia group, the administration of exogenous surfactant was able to reduce lung inflammation through a reduction in the influx of neutrophils and inflammatory biomarkers such as TNF, IL-17, and HMGB1 expression. The antioxidant activity prevented oxidative damage by reducing lipid peroxidation and protein carbonylation and increasing superoxide dismutase activity when compared to the hyperoxia group. Conclusion: Our results offer new perspectives on the effects and the mechanism of exogenous surfactant in protecting the airway and lungs, in oxygen-rich lung microenvironment, against oxidative damage and aggravation of acute inflammation induced by hyperoxia.
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...
International Journal of Experimental Pathology, 2017
Toxoplasmosis represents one of the most common zoonoses worldwide. Its agent, Toxoplasma gondii,... more Toxoplasmosis represents one of the most common zoonoses worldwide. Its agent, Toxoplasma gondii, causes a severe innate pro-inflammatory response. The indigenous intestinal microbiota promotes host animal homoeostasis and may protect the host against pathogens. Germ-free (GF) animals provide an important tool for the study of interactions between host and microbiota. In this study, we assessed the role of indigenous microorganisms in disease development utilizing a murine toxoplasmosis model, which includes conventional (CV) and GF NIH Swiss mice. CV and GF mice orally inoculated with T. gondii had similar survival curves. However, disease developed differently in the two animal groups. In CV mice, intestinal permeability increased and levels of intestinal pro-inflammatory cytokines were altered. In GF animals, there were discrete epithelial degenerative changes and mucosal oedema, but the liver and lungs displayed significant lesions. We conclude that, despite similar survival curves, CV animals succumb to an exaggerated inflammatory response, whereas GF mice fail to produce an adequate systemic response.
Journal of Neuroinfectious Diseases, 2016
Chagas disease is a chronic disorder caused by the Trypanosoma cruzi protozoan. The infection cau... more Chagas disease is a chronic disorder caused by the Trypanosoma cruzi protozoan. The infection causes alterations to the enteric nervous system such as megaesophagus and megacolon. There is evidence of denervation of myenteric ganglia. The intense parasitism of acute phase affects neuronal integrity but contrasts with the absence of parasites and the discreet inflammatory process of chronic phase, indicating a progressive injury mechanism that needs to be better understood in the megacolons. The potential selectivity of enteric neurons classes affected by the progression of the disease is not yet clear. Nitrergic neurons which co-localize other neurotransmitters represent the most common inhibitory neuron of the ENS. Recently a chronic stage of the Chagas disease was reproduced experimentally in a suitable murine model of megacolon. Considering the limitation of studying human intestine and the controversy on the pattern of nNOS involvement in chagasic megacolon, we decided to assess the nitrergic neurons in the myenteric plexus of mice. We used antibodies against structural protein gene product 9.5 (PGP 9.5) and functional neuronal nitric oxide synthase (n-NOS) at the acute and chronic phase of the disease to quantify myenteric ganglionar neurons in the colon of infected and non-infected mice. We found a reduction in the ganglionar number of neurons detected by anti-protein gene product 9.5 antibodies in colon from mice at the chronic stage. However, the number of nitrergic neurons per ganglia remained unchanged along the acute to phase chronic of the disease. Our findings indicate a long-term preservation of nitregic neurons detrimental to other classes of enteric in our model of experimental Chagas disease. We propose that differential loss of enteric neurons is at least one of the structural substrate for the development of the longterm morphfunctional changes that lead to the megacolon.
Beneficial Microbes, 2016
Indigenous microbiota plays a crucial role in the development of several intestinal diseases, inc... more Indigenous microbiota plays a crucial role in the development of several intestinal diseases, including mucositis. Gastrointestinal mucositis is a major and serious side effect of cancer therapy, and there is no effective therapy for this clinical condition. However, some probiotics have been shown to attenuate such conditions. To evaluate the effects of Saccharomyces cerevisiae UFMG A-905 (Sc-905), a potential probiotic yeast, we investigated whether pre- or post-treatment with viable or inactivated Sc-905 could prevent weight loss and intestinal lesions, and maintain integrity of the mucosal barrier in a mucositis model induced by irinotecan in mice. Only post-treatment with viable Sc-905 was able to protect mice against the damage caused by chemotherapy, reducing the weight loss, increase of intestinal permeability and jejunal lesions (villous shortening). Besides, this treatment reduced oxidative stress, prevented the decrease of goblet cells and stimulated the replication of ce...
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 |
International Journal of Infectious Diseases, 2016
Objectives: Different methods for the classification of leprosy have been proposed since the 1930... more Objectives: Different methods for the classification of leprosy have been proposed since the 1930s. The aim of this study was to compare the current methods at a referral center in Brazil. Methods: The World Health Organization (WHO) operational classification was compared to the Ridley and Jopling classification, the Madrid classification, and a classification based on the number of body areas affected by skin and/or neural lesions (NBAA). The correlation between the clinical and histopathological components of the Ridley and Jopling classification was assessed. Results: The agreement between the WHO operational classification and the Ridley and Jopling classification was 77.6% (kappa = 0.53). The WHO operational classification tended to overestimate the number of multibacillary patients. The WHO operational classification showed its best agreement with the NBAA. There was perfect agreement between the clinical and histopathological Ridley and Jopling classification in 46.9% of the patients. Conclusions: The agreement between the WHO operational classification and the Ridley and Jopling classification was better than any other purely clinical classification, reinforcing the importance and simplicity of the operational method. Although major disagreement between the clinical and histopathological Ridley and Jopling classification was uncommon, perfect agreement occurred in less than half of the cases, and was even lower for the borderline lepromatous and tuberculoid forms. Possible reasons for the differences are discussed; these showed that there may be room for improvement in the Ridley and Jopling classification histopathological criteria.
Microbiology (Reading, England), Jan 28, 2015
Mucositis is one of the most debilitating side effects of chemotherapy and some previous studies ... more Mucositis is one of the most debilitating side effects of chemotherapy and some previous studies suggest a role for indigenous microbiota in the course of this pathology. Therefore, the aim of our study was to evaluate the differences in phenotype between germ-free (GF) and conventional (CV) mice, and the role of β-glucuronidase-producing bacteria in the development of irinotecan treatment in a murine model. After mucositis induction, CV mice showed a significant increase in all inflammatory parameters when compared to GF mice. CV animals also showed more lesions of intestinal epithelium, coherent with their higher intestinal permeability. The conventionalization of GF animals reversed their phenotype to that found in CV mice. In addition, gnotobiotic mice monoassociated with an Escherichia coli strain producing β-glucuronidase showed an increased permeability when compared to gnotobiotic mice monoassociated with an E. coli strain deleted for the gene encoding β-glucuronidase, but t...
European Journal of Immunology, 2014
During oral infection, mucosal immunity assumes a predominant role. Here, we addressed the role o... more During oral infection, mucosal immunity assumes a predominant role. Here, we addressed the role of mast cells (MCs), which are mainly located in mucosa during oral infection with Toxoplasma gondii, using MC-deficient (W/W v) mice. We show that in the absence of MCs the resistance of W/W v mice to oral infection was considerably reduced. W/W v mice uniformly succumbed within 15 days of infection after administration of cysts of the ME49 strain of T. gondii. The rapid lethality of T. gondii in W/W v mice correlated with a delayed Th1-cell response, since IFN-γ and IL-12 levels peaked in the later phase of the infection. In vitro, BM-derived MCs were able to recognize parasite lysate in a MyD88-dependent way, reaffirming the role of this TLR adapter in immune responses to T. gondii. The importance of MCs in vivo was confirmed when W/W v mice reconstituted with BM-derived MCs from control mice retrieved an early strong Th1-cell response and specially a significant IL-12 production. In conclusion, MCs play an important role for the development of a protective immune response during oral infection with T. gondii.
Journal of Neuroinflammation, 2014
Background Herpes simplex 1 (HSV-1) causes various human clinical manifestations, ranging from si... more Background Herpes simplex 1 (HSV-1) causes various human clinical manifestations, ranging from simple cold sores to encephalitis. Innate immune cells recognize pathogens through Toll-like receptors (TLRs), thus initiating the immune response. Previously, we demonstrated that the immune response against HSV-1 is dependent on TLR2 and TLR9 expression and on IFN gamma production in the trigeminal ganglia (TG) of infected mice. In this work, we further investigated the cells, molecules, and mechanisms of HSV-1 infection control, especially those that are TLR-dependent. Methods C57BL/6 wild-type (WT), TLR2−/−, TLR9−/−, and TLR2/9−/− mice were intranasally infected with HSV-1. On the viral peak day, the TG and brains were collected from mice and TLR expression was measured in the TG and brain and inducible nitric oxide synthase (iNOS) expression was measured in the TG by real-time PCR. Immunofluorescence assays were performed in mice TG to detect iNOS production by F4/80+ cells. Intraperi...