National Institute of Cardiology

Warsaw, Poland

National Institute of Cardiology

Warsaw, Poland
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Maeda T.,Texas A&M University | Maeda T.,Kyushu Institute of Technology | Garcia-Contreras R.,National Institute of Cardiology | Garcia-Contreras R.,VU University Amsterdam | And 7 more authors.
ISME Journal | Year: 2012

Quorum sensing (QS) is the regulation of gene expression in response to the concentration of small signal molecules, and its inactivation has been suggested to have great potential to attenuate microbial virulence. It is assumed that unlike antimicrobials, inhibition of QS should cause less Darwinian selection pressure for bacterial resistance. Using the opportunistic pathogen Pseudomonas aeruginosa, we demonstrate here that bacterial resistance arises rapidly to the best-characterized compound that inhibits QS (brominated furanone C-30) due to mutations that increase the efflux of C-30. Critically, the C-30-resistant mutant mexR was more pathogenic to Caenorhabditis elegans in the presence of C-30, and the same mutation arises in bacteria responsible for chronic cystic fibrosis infections. Therefore, bacteria may evolve resistance to many new pharmaceuticals thought impervious to resistance. © 2012 International Society for Microbial Ecology All rights reserved.

Martinez-Lavin M.,National Institute of Cardiology | Amezcua-Guerra L.,National Institute of Cardiology
Clinical Rheumatology | Year: 2017

This article critically reviews HPV vaccine serious adverse events described in pre-licensure randomized trials and in post-marketing case series. HPV vaccine randomized trials were identified in PubMed. Safety data were extracted. Post-marketing case series describing HPV immunization adverse events were reviewed. Most HPV vaccine randomized trials did not use inert placebo in the control group. Two of the largest randomized trials found significantly more severe adverse events in the tested HPV vaccine arm of the study. Compared to 2871 women receiving aluminum placebo, the group of 2881 women injected with the bivalent HPV vaccine had more deaths on follow-up (14 vs. 3, p = 0.012). Compared to 7078 girls injected with the 4-valent HPV vaccine, 7071 girls receiving the 9-valent dose had more serious systemic adverse events (3.3 vs. 2.6%, p = 0.01). For the 9-valent dose, our calculated number needed to seriously harm is 140 (95% CI, 796–53). The number needed to vaccinate is 1757 (95% CI, 131 to infinity). Practically, none of the serious adverse events occurring in any arm of both studies were judged to be vaccine-related. Pre-clinical trials, post-marketing case series, and the global drug adverse reaction database (VigiBase) describe similar post-HPV immunization symptom clusters. Two of the largest randomized HPV vaccine trials unveiled more severe adverse events in the tested HPV vaccine arm of the study. Nine-valent HPV vaccine has a worrisome number needed to vaccinate/number needed to harm quotient. Pre-clinical trials and post-marketing case series describe similar post-HPV immunization symptoms. © 2017 International League of Associations for Rheumatology (ILAR)

Castro R.D.A.L.,National Institute of Cardiology | Portela M.C.,Oswaldo Cruz Foundation | Leao A.T.,Federal University of Rio de Janeiro | De Vasconcellos M.T.L.,Brazilian Institute of Geography and Statistics
Community Dentistry and Oral Epidemiology | Year: 2011

Objectives: The objective of this study was to assess the association between oral health-related quality of life (OHRQoL), measured through the Child-OIDP, and demographic characteristics, self-reported oral problems, and clinical oral health measures, among 11- to 12-year-old school children in the city of Rio de Janeiro, Brazil. Methods: A cross-sectional study was conducted, having as its target population 11- and 12-year-old students of both sexes, formally enrolled in 6- and 7-year school classes at public schools. A probabilistic sample with complex design was used. OHRQoL was assessed by the Brazilian version of Child-OIDP. Oral exams were conducted, and the presence of dental biofilm, gingival bleeding, DMFT, fluorosis, enamel defects, dental trauma, and malocclusion were recorded. Results: A total of 571 school children participated with a mean age of 12.0 years and 95% confidence interval (95% CI) from 11.9 to 12.1. A total of 88.7% of the school children presented the impact of oral problems in at least one of the eight daily performances. The activities that had most impacts were eating (81.3%), cleaning mouth (40.5%), and smiling (32.2%). The mean Child-OIDP index was 7.1 with 95% CI from 6.2 to 8.1. The highest scores were in relation to eating (mean = 25.0; 95% CI from 22.4 to 27.6), cleaning mouth (mean = 12.0; 95% CI from 9.1 to 14.9), and smiling (mean = 10.0; 95% CI from 7.5 to 12.5). In the logistic regression model, the Child-OIDP was associated with dental caries experience and with the perception of sensitive teeth, perception of gingival bleeding, and perception of inadequate position of the teeth. In the multinomial regression, we found that the odds of having higher levels of Child-OIDP were positively associated with dental caries experience. Self-reported dental caries, mobile milk teeth, tooth position, bleeding gums, and bad breath were associated with worst OHRQoL. Conclusions: It can be concluded that there is an association between dental caries experience and the Child-OIDP index. This association indicates the impact of this condition on the quality of life of school children. Moreover, the Child-OIDP index is explained more by self-reported oral problems than by clinical normative measures. © 2010 John Wiley & Sons A/S.

Sorensen K.,Maastricht University | Van Den Broucke S.,Catholic University of Louvain | Fullam J.,University College Dublin | Doyle G.,University College Dublin | And 3 more authors.
BMC Public Health | Year: 2012

Background: Health literacy concerns the knowledge and competences of persons to meet the complex demands of health in modern society. Although its importance is increasingly recognised, there is no consensus about the definition of health literacy or about its conceptual dimensions, which limits the possibilities for measurement and comparison. The aim of the study is to review definitions and models on health literacy to develop an integrated definition and conceptual model capturing the most comprehensive evidence-based dimensions of health literacy. Methods. A systematic literature review was performed to identify definitions and conceptual frameworks of health literacy. A content analysis of the definitions and conceptual frameworks was carried out to identify the central dimensions of health literacy and develop an integrated model. Results: The review resulted in 17 definitions of health literacy and 12 conceptual models. Based on the content analysis, an integrative conceptual model was developed containing 12 dimensions referring to the knowledge, motivation and competencies of accessing, understanding, appraising and applying health-related information within the healthcare, disease prevention and health promotion setting, respectively. Conclusions: Based upon this review, a model is proposed integrating medical and public health views of health literacy. The model can serve as a basis for developing health literacy enhancing interventions and provide a conceptual basis for the development and validation of measurement tools, capturing the different dimensions of health literacy within the healthcare, disease prevention and health promotion settings. © 2012 Sorensen et al; BioMed Central Ltd.

Maeda T.,Kyushu Institute of Technology | Yoshimura T.,Kyushu Institute of Technology | Garcia-Contreras R.,National Institute of Cardiology | Ogawa H.I.,Kyushu Institute of Technology
Bioresource Technology | Year: 2011

A novel protease secreted by Brevibacillus sp. KH3 isolated from excess sludge at 50 °C and used as a sludge-lysing strain was investigated in this study. Sludge reduction was minimized by protease inhibitors and a 40-kDa protease, which significantly contributed to this sludge-reducing activity, was purified as the target protein. The final purified protease demonstrated 92-fold higher specific activity than the initial crude extracts. The sludge-reducing efficiency deteriorated relative to decreased protease activity triggered by EDTA; thus, the purified protease was a causative agent in reducing excess sludge. The 40-kDa protease was a serine metalloprotease and showed the highest activity at 50 °C and pH 8.0, and the activity was enhanced in the presence of calcium ions, indicating that the purified protease contained calcium ion. Furthermore, this 40-kDa protease inhibited biofilm formation in excess sludge. These results imply that sludge reduction is because of reduction of biofilm formation in excess sludge. © 2011 Elsevier Ltd.

Garcia-Contreras R.,National Institute of Cardiology | Nunez-Lopez L.,National Institute of Cardiology | Jasso-Chavez R.,National Institute of Cardiology | Kwan B.W.,Pennsylvania State University | And 4 more authors.
ISME Journal | Year: 2015

Quorum sensing (QS) coordinates the expression of virulence factors and allows bacteria to counteract the immune response, partly by increasing their tolerance to the oxidative stress generated by immune cells. Despite the recognized role of QS in enhancing the oxidative stress response, the consequences of this relationship for the bacterial ecology remain unexplored. Here we demonstrate that QS increases resistance also to osmotic, thermal and heavy metal stress. Furthermore a QS-deficient lasR rhlR mutant is unable to exert a robust response against H 2 O 2 as it has less induction of catalase and NADPH-producing dehydrogenases. Phenotypic microarrays revealed that the mutant is very sensitive to several toxic compounds. As the anti-oxidative enzymes are private goods not shared by the population, only the individuals that produce them benefit from their action. Based on this premise, we show that in mixed populations of wild-type and the mexR mutant (resistant to the QS inhibitor furanone C-30), treatment with C-30 and H 2 O 2 increases the proportion of mexR mutants; hence, oxidative stress selects resistance to QS compounds. In addition, oxidative stress alone strongly selects for strains with active QS systems that are able to exert a robust anti oxidative response and thereby decreases the proportion of QS cheaters in cultures that are otherwise prone to invasion by cheats. As in natural environments stress is omnipresent, it is likely that this QS enhancement of stress tolerance allows cells to counteract QS inhibition and invasions by social cheaters, therefore having a broad impact in bacterial ecology. © 2015 International Society for Microbial Ecology All rights reserved.

Ralph S.J.,Griffith University | Rodriguez-Enriquez S.,National Institute of Cardiology | Neuzil J.,Griffith University | Neuzil J.,Academy of Sciences of the Czech Republic | Moreno-Sanchez R.,National Institute of Cardiology
Molecular Aspects of Medicine | Year: 2010

Mitochondria are emerging as idealized targets for anti-cancer drugs. One reason for this is that although these organelles are inherent to all cells, drugs are being developed that selectively target the mitochondria of malignant cells without adversely affecting those of normal cells. Such anti-cancer drugs destabilize cancer cell mitochondria and these compounds are referred to as mitocans, classified into several groups according to their mode of action and the location or nature of their specific drug targets. Many mitocans selectively interfere with the bioenergetic functions of cancer cell mitochondria, causing major disruptions often associated with ensuing overloads in ROS production leading to the induction of the intrinsic apoptotic pathway. This in-depth review describes the bases for the bioenergetic differences found between normal and cancer cell mitochondria, focussing on those essential changes occurring during malignancy that clinically may provide the most effective targets for mitocan development. A common theme emerging is that mitochondrially mediated ROS activation as a trigger for apoptosis offers a powerful basis for cancer therapy. Continued research in this area is likely to identify increasing numbers of novel agents that should prove highly effective against a variety of cancers with preferential toxicity towards malignant tissue, circumventing tumor resistance to the other more established therapeutic anti-cancer approaches. Crown Copyright © 2009.

Ralph S.J.,Griffith University | Rodriguez-Enriquez S.,National Institute of Cardiology | Neuzil J.,Griffith University | Neuzil J.,Academy of Sciences of the Czech Republic | And 2 more authors.
Molecular Aspects of Medicine | Year: 2010

The role of oncoproteins and tumor suppressor proteins in promoting the malignant transformation of mammalian cells by affecting properties such as proliferative signalling, cell cycle regulation and altered adhesion is well established. Chemicals, viruses and radiation are also generally accepted as agents that commonly induce mutations in the genes encoding these cancer-causing proteins, thereby giving rise to cancer. However, more recent evidence indicates the importance of two additional key factors imposed on proliferating cells that are involved in transformation to malignancy and these are hypoxia and/or stressful conditions of nutrient deprivation (e.g. lack of glucose). These two additional triggers can initiate and promote the process of malignant transformation when a low percentage of cells overcome and escape cellular senescence. It is becoming apparent that hypoxia causes the progressive elevation in mitochondrial ROS production (chronic ROS) which over time leads to stabilization of cells via increased HIF-2alpha expression, enabling cells to survive with sustained levels of elevated ROS. In cells under hypoxia and/or low glucose, DNA mismatch repair processes are repressed by HIF-2alpha and they continually accumulate mitochondrial ROS-induced oxidative DNA damage and increasing numbers of mutations driving the malignant transformation process. Recent evidence also indicates that the resulting mutated cancer-causing proteins feedback to amplify the process by directly affecting mitochondrial function in combinatorial ways that intersect to play a major role in promoting a vicious spiral of malignant cell transformation. Consequently, many malignant processes involve periods of increased mitochondrial ROS production when a few cells survive the more common process of oxidative damage induced cell senescence and death. The few cells escaping elimination emerge with oncogenic mutations and survive to become immortalized tumors. This review focuses on evidence highlighting the role of mitochondria as drivers of elevated ROS production during malignant transformation and hence, their potential as targets for cancer therapy. The review is organized into five main sections concerning different aspects of " mitochondrial malignancy" The first concerns the functions of mitochondrial ROS and its importance as a pacesetter for cell growth versus senescence and death. The second considers the available evidence that cellular stress in the form of hypoxic and/or hypoglycaemic conditions represent two of the major triggering events for cancer and how oncoproteins reinforce this process by altering gene expression to bring about a common set of changes in mitochondrial function and activity in cancer cells. The third section presents evidence that oncoproteins and tumor suppressor proteins physically localize to the mitochondria in cancer cells where they directly regulate malignant mitochondrial programs, including apoptosis. The fourth section covers common mutational changes in the mitochondrial genome as they relate to malignancy and the relationship to the other three areas. The last section concerns the relevance of these findings, their importance and significance for novel targeted approaches to anti-cancer therapy and selective triggering in cancer cells of the mitochondrial apoptotic pathway. © 2010.

Martinez-Lavin M.,National Institute of Cardiology
Pain Research and Treatment | Year: 2012

Fibromyalgia is a painful stress-related disorder. A key issue in fibromyalgia research is to investigate how distress could be converted into pain. The sympathetic nervous system is the main element of the stress response system. In animal models, physical trauma, infection, or distressing noise can induce abnormal connections between the sympathetic nervous system and the nociceptive system. Dorsal root ganglia sodium channels facilitate this type of sympathetic pain. Similar mechanisms may operate in fibromyalgia. Signs of sympathetic hyperactivity have been described in this condition. Genetic factors and/or distressful lifestyle may lead to this state of sympathetic hyperactivity. Trauma and infection are recognized fibromyalgia triggers. Women who suffer from fibromyalgia have catecholamine-evoked pain. Sympathetic dysfunction may also explain nonpain-related fibromyalgia symptoms. In conclusion, in fibromyalgia, distress could be converted into pain through forced hyperactivity of the sympathetic component of the stress response system. © 2012 Manuel Martinez-Lavin.

Buelna-Chontal M.,National Institute of Cardiology | Zazueta C.,National Institute of Cardiology
Cellular Signalling | Year: 2013

Moderate concentrations of reactive oxygen species (ROS) are produced by diverse sources under physiological conditions. At such low levels, these molecules may act as upstream mediators of relevant signaling pathways; however an increase in their concentration with respect to the antioxidant system activity, changes their redox signaling function into a deleterious role. Thus, cell health depends, at least in part, on redox balance. This review includes global aspects of oxygen chemistry, ROS generation, antioxidant system, and redox signaling. It is also focused on the description of two relevant redox-sensitive transcription factors: nuclear factor erythroid 2-related factor 2 (Nrf2), which may be a potential target to confer cell protection, and nuclear factor κB (NF-κB), which is involved in deleterious effects in the cell. Finally, recent findings on the interplay between both factors for the development of different pathologies are discussed. © 2013 Elsevier Inc.

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