Lambertucci F.,CONICET |
Motino O.,Institute Investigaciones Biomedicas Alberto Sols |
Villar S.,Institute Inmunologia |
Rigalli J.P.,CONICET |
And 8 more authors.
Toxicology and Applied Pharmacology | Year: 2017
Molecular mechanisms on sepsis progression are linked to the imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity. Previous studies demonstrated that benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, has immunomodulatory effects, increasing survival in C57BL/6 mice in a model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). The mechanism by which BZL inhibits inflammatory response in sepsis is poorly understood. Also, our group recently reported that BZL is able to activate the nuclear factor erytroide-derived 2-Like 2 (NRF2) in vitro. The aim of the present work was to delineate the beneficial role of BZL during sepsis, analyzing its effects on the cellular redox status and the possible link to the innate immunity receptor TLR4. Specifically, we analyzed the effect of BZL on Nrf2 regulation and TLR4 expression in liver of mice 24 hours post-CLP. BZL was able to induce NRF2 nuclear protein localization in CLP mice. Also, we found that protein kinase C (PKC) is involved in the NRF2 nuclear accumulation and induction of its target genes. In addition, BZL prompted a reduction in hepatic CLP-induced TLR4 protein membrane localization, evidencing its immunomodulatory effects. Together, our results demonstrate that BZL induces hepatic NRF2 activation with the concomitant increase in the antioxidant defenses, and the attenuation of inflammatory response, in part, by inhibiting TLR4 expression in a murine model of sepsis. © 2016 Elsevier Inc.
Morosano M.E.,National University of Rosario |
Masoni A.M.,National University of Rosario |
Tamano V.F.,National University of Rosario |
Pezzotto S.M.,Institute Inmunologia
Revista Medica de Rosario | Year: 2014
The incidence rates of hip fractures vary between neighboring countries in the same continent, between different regions of the same country, and even among different neighborhoods in the same city. The aim of this study was to determine whether there were differences in the incidence rates of hip fracture in the 6 districts in which the city of Rosario (province of Santa Fe, Argentina: Population 1 million) is divided. We also tried to ascertain whether there are environmental (health indicators) or socioeconomic factors that could explain the differences. The study had an ecological design. Global incidence rates specific for sex and age groups, and the truncated rates were calculated and adjusted in each municipal district of Rosario. The social health indicators studied were mortality, unmet basic needs, housing, inhabitants/hectare, mothers under age 20, low birth weight, settlements, open spaces. Multivariate analysis considering rates as the dependent variable and social and health indicators, gender and age as independent variables, using Poisson regression and calculating the relative risk (rate ratio) was applied. As results of this study, we conclude that the incidence of hip fracture does not differ between population districts of Rosario, and that no population groups were identified presenting an increased risk for this complication of osteoporosis, based on their place of residence, health conditions or socioeconomic characteristics.
Association of tumor necrosis factor-alpha with fibronectin stimulates ex vivo migration of T lymphocytes in patients with severe chagasic myocarditis [La asociación de factor de necrosis tumoral alfa con fibronectina estimula la migración ex vivo de linfocitos T de pacientes con miocarditis chagásica severa]
Berbert L.R.,Instituto Oswaldo Cruz |
Manarin R.,Institute Inmunologia |
Gonzalez F.,Institute Inmunologia |
Savino W.,Instituto Oswaldo Cruz |
And 2 more authors.
Revista de la Federacion Argentina de Cardiologia | Year: 2012
During T. cruzi infection, there is a production of inflammatory mediators that seems to be related to the infiltrating ability of T lymphocytes and the subsequent development of chronic chagasic myocarditis (CCM), like Tumor Necrosis Factor-alpha (TNF-α). Previous data obtained from experimental models reinforce the view about the key role of TNF-α on migration processes that drive autoreactive cells into the heart. On this basis we evaluated the role of TNF-α in T lymphocyte migration processes and the possible association between the different migration profiles of chagasic patients and the degree of MCC that they present. Peripheral blood mononuclear cells (PBMC) were obtained from healthy individuals (Co) or chagasic patients with different degrees of cardiac involvement (no apparent pathology or symptomatic with mild to moderate or severe cardiophaty/ n = 8-13/group). We evaluated the migratory capacity of T cells in response to fibronectin (FN) in combination or not to TNF-α using ex vivo migration techniques involving transwell chambers, followed by detection of migrant cells by flow cytometry. The assessment of circulating levels of TNF-α in patients showed that their serum concentrations increased with the severity of the CCM. The results of ex vivo migration studies showed that TNF-α increased the migration of both PBMC as T CD4+ and CD8+ lymphocytes in patients with severe heart disease. Data suggest an association between systemic levels of TNF-α with the migratory and infiltrating ability of T lymphocytes.
PubMed | CONICET, Institute Investigaciones Biomedicas Alberto Sols and Institute Inmunologia
Type: | Journal: Toxicology and applied pharmacology | Year: 2016
Molecular mechanisms on sepsis progression are linked to the imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity. Previous studies demonstrated that benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, has immunomodulatory effects, increasing survival in C57BL/6 mice in a model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). The mechanism by which BZL inhibits inflammatory response in sepsis is poorly understood. Also, our group recently reported that BZL is able to activate the nuclear factor erytroide-derived 2-Like 2 (NRF2) in vitro. The aim of the present work was to delineate the beneficial role of BZL during sepsis, analyzing its effects on the cellular redox status and the possible link to the innate immunity receptor TLR4. Specifically, we analyzed the effect of BZL on Nrf2 regulation and TLR4 expression in liver of mice 24hours post-CLP. BZL was able to induce NRF2 nuclear protein localization in CLP mice. Also, we found that protein kinase C (PKC) is involved in the NRF2 nuclear accumulation and induction of its target genes. In addition, BZL prompted a reduction in hepatic CLP-induced TLR4 protein membrane localization, evidencing its immunomodulatory effects. Together, our results demonstrate that BZL induces hepatic NRF2 activation with the concomitant increase in the antioxidant defenses, and the attenuation of inflammatory response, in part, by inhibiting TLR4 expression in a murine model of sepsis.
de Sanctis J.B.,Institute Inmunologia |
Mijares M.,Central University of Venezuela |
Suarez A.,Central University of Venezuela |
Compagnone R.,Central University of Venezuela |
And 3 more authors.
Recent Patents on Inflammation and Allergy Drug Discovery | Year: 2010
Thalidomide and its immunomodulatory imide drugs (IMiDs) analogues CC-5013 (Revlimid™, Lenalidomide) and CC-4047 (Actimid™, Pomalidomide) have been used as anti-inflammatory and anticancerous drugs in the recent years. Thalidomide and IMiDs inhibit the cytokines tumour necrosis factor-(TNF-), interleukins (IL) 1, 6, 12, and granulocyte macrophage-colony stimulating factor (GM-CSF). They also costimulate primary human T, NKT and NK lymphocytes inducing their proliferation, cytokine production, and cytotoxic activity. On the other hand, the compounds are anti-angiogenic, anti-proliferative, and pro-apoptotic. Thalidomide analogues have been used as inhibitors of glucosidase and could be potential drugs for diabetes treatment. In this review, we explore the current trend of the different structures, the new patents, and the possible new applications in different pathologies. © 2010 Bentham Science Publishers Ltd.
Saenz B.,National Autonomous University of Mexico |
Hernandez-Pando R.,Instituto Nacional Of Ciencias Medicas Y Of La Nutricion |
Fragoso G.,National Autonomous University of Mexico |
Bottasso O.,Institute Inmunologia |
Cardenas G.,Instituto Nacional Of Neurologia Y Neurocirugia
Tuberculosis | Year: 2013
Tuberculosis (TB) is still a common infectious disease in developing countries, but it is also re-emerging in industrialized nations due to the HIV/AIDS pandemic. In addition to bacillary virulence, the host immune response plays a major role in the development of an active disease (either as a primary infection or reactivation) and in controlling the infection. Even though several mechanisms are involved in regulating the human immune response, biological environment seems to be determinant. In this context, the integrated neuro-immune-endocrine system strongly influences TB clinical outcome. One of the most important clinical aspects of TB is shown when the infection locates in the central nervous system (CNS), in which a very different set of immune responses is induced. Herein we review several aspects of the paradoxical immune response triggered during CNS-TB infection, and discuss the implications of this response in the cerebral infection outcome. © 2012 Elsevier Ltd. All rights reserved.
Pezzotto S.M.,Institute Inmunologia |
Morosano M.E.,National University of Rosario |
Chapo G.,National University of Rosario |
Menoyo I.,National University of Rosario |
And 2 more authors.
Revista Medica de Rosario | Year: 2010
Wedge fractures constitute a relevant consequence of osteoporosis due to the important morbidity and the heavy burden for the health system that they generate. The use of morphometric criteria to define them is not currently applied in our midst. Therefore, many significant vertebral deformities probably remain undetected in the daily clinical setting. The purpose of this paper was to compare two morphometric criteria to determine the prevalence of wedge vertebral fractures in dorsal spine radiographs corresponding to a sample of 164 asymptomatic, untreated postmenopausal women, and to evaluate the reliability of the measurements. Criterion 1 (Genant): A wedge fracture is defined when the vertebral body's anterior height is reduced 20% or more compared to the posterior height. Criterion 2: A fracture is defined when the relation anterior height/posterior height of each vertebral body is below a cut-point given by the average minus two standard deviations of that relation, corresponding to the same vertebral body in the whole sample. Vertebral morphometry was performed in 1,476 vertebral bodies using a Vernier-type caliper. Anterior and posterior heights as well as the superior margins were measured, completing 5,346 measurements (including 918 duplicates to evaluate inter and intra-observer variation). Cohen's Kappa coefficient and Intra-Class Correlation Coefficient (ICC) were used to test the agreement between both criteria; 95% confidence intervals (CI) were calculated. The prevalences of vertebral wedge fracture were 25.6% for Criterion 1 (Genant), and 23.7% for Criterion 2. Agreement between both criteria was statistically significant (K=0.853, IC=0.76-0.95; p<0.001). ICC expressing intra-observer variation agreement was 0.996 (CI=0.994-0.998), significantly different from zero (p<0.00001). In the inter-observer analysis the ICC obtained was 0.994 (CI= 0.992-0.995; p<0.00001). In both instances the degree of agreement was almost perfect. The vertebral wedge fracture prevalences derived from both criteria are not satistically different, and are similar to those reported from other places worldwide. Our present data indicate that the less complex Genant's criterion would be very useful for the evaluation of wedge vertebral deformities in the everyday clinical setting.
Dagatti M.S.,Institute Inmunologia |
Compagnucci A.B.,Institute Inmunologia |
Pezzotto S.M.,Institute Inmunologia |
Pezzotto S.M.,National University of Rosario
Revista Chilena de Nutricion | Year: 2011
A case-control study was carried out in order to analyze the association between diet and risk of non melanoma skin cancer -basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), with adjustments for demographic, anthropometric and phenotypic characteristics, sunburns history, skin cancer family history, sun-exposure history and skin sensitivity to sun exposure. A full-body skin examination was performed. Dietary data were obtained applying a standardized semi-quantitative questionnaire of consumption frequency. Cases (n=27; age: 65,5±15,1 years) and controls (n=37; age: 63,9±12,3 years) were attended at the same facilities. A decreased risk of BCC and SCC tumors (Adjusted Odd Ratio=0.10; IC 95%= 0.02-0.63; p=0.01) was found for high intakes of green leafy vegetables (more than 40 gr/day). However, results obtained for fruits, cruciferous, vitamin A and carotene-rich vegetables and other vegetables were not statistically significant.
Moreno M.,Consulta de Otorrinolaringologia |
Tassinari P.,Institute Inmunologia
Informe Medico | Year: 2012
Oral antihistaminics can be classified into first and second generation agents, according to its pharmacokinetics, pharmacodynamics and adverse events profile. Mast cells and basophil leukocytes store histamine within intracellular granules, releasing this amine upon stimulation by IgE binding to the cell membrane. Histamine exerts its effects through interaction with four different receptors subtypes: H1, H2, H3 and H4, coupled to a G protein. H1 receptors are found in endothelial and smooth muscle vascular cells, promoting histamine-mediated vasodilation and vascular permeability; however rhinorrohea is also stimulated by the parasympathetic innervation of secretory glands. On the other hand, H2 receptors present in submucous glands and epithelial cells of nasal mucosae also contribute to rhinitis symptoms. There are two therapeutic categories of H1 antihistaminics; first and second generation compounds; the later ones were developed 1980 and are poorly sedative; the first group can cross the blood brain barrier because of its lipophylicity and have a pronounced sedative property. Second generation antihistaminics reduce both phases of the allergic reaction, showing antiallergic and anti-inflammatory activity mediated by calcium channel blocking properties, exerted on mast cells and basophil leukocytes, which in turn inhibit expression of intercellular-1 adhesion molecule in nasal epithelia.