267 research outputs found
Role of TNF-a in host immune response in tuberculous pleuritis
Tumour Necrosis Factor (TNF)-a, a pro-inflammatory
cytokine has a dual role in host immunity and
immunopathology of tuberculosis and is considered to
be pivotal for determining the clinical course of the
disease, either beneficial or detrimental. The assessment
of TNF-a in pleural tuberculosis will help us to
understand its role in host defence mechanism against
Mycobacterium tuberculosis (MTB) infection. In this
study, TNF-a and IFN-g levels were measured in plasma
and pleural fluid of both tuberculosis (TB) and non-
TB patients and in the supernatants of blood and
pleural fluid mononuclear cells (PBMCs and PFMCs)
stimulated in vitro with PPD, culture filtrate and heatkilled
(MTB). In addition, apoptosis induced by PPD
and MTB was also studied. TNF-a and IFN-g were
significantly elevated in pleural fluid than in plasma
of pleural tuberculosis patients, suggesting the compartmentalization
of Th1 cytokine-secreting cells at
the site of disease. In vitro stimulation of PFMCs with
PPD and MTB showed a significant increase in these
cytokine levels and also enhanced apoptosis of these
cells. This increase in TNF-a levels may contribute to
the containment of infection by synergizing with IFN-
g to activate infected macrophages or by the regulation
of T-cell apoptosis
5-hydroxymethyl-cytosine enrichment of non-committed cells is not a universal feature of vertebrate development
5-hydroxymethyl-cytosine (5-hmC) is a cytosine modification that is relatively abundant in mammalian pre-implantation embryos and embryonic stem cells (ESC) derived from mammalian blastocysts. Recent observations imply that both 5-hmC and Tet1/2/3 proteins, catalyzing the conversion of 5-methyl-cytosine to 5-hmC, may play an important role in self renewal and differentiation of ESCs. Here we assessed the distribution of 5-hmC in zebrafish and chick embryos and found that, unlike in mammals, 5-hmC is immunochemically undetectable in these systems before the onset of organogenesis. In addition, Tet1/2/3 transcripts are either low or undetectable at corresponding stages of zebrafish development. However, 5-hmC is enriched in later zebrafish and chick embryos and exhibits tissue-specific distribution in adult zebrafish. Our findings show that 5-hmC enrichment of non-committed cells is not a universal feature of vertebrate development and give insights both into evolution of embryonic pluripotency and the potential role of 5-hmC in its regulation. © 2012 Landes Bioscience
Phosphate regulates expression of SIBLINGs and MMPs in cementoblasts
Introduction: Cementoblasts, the cells responsible for tooth root cementum formation, are especially sensitive to local phosphate and pyrophosphate during development, as evidenced by cementum phenotypes resulting from altered phosphate/pyrophosphate distribution. SIBLING family members BSP, OPN, and DMP-1 are regulated by phosphate in cementoblasts and have been shown to activate three specific matrix metalloproteinase (MMP) partners: MMP2, MMP3, and MMP9, respectively, in vitro. The aim of this study was to examine regulatory effects of phosphate on SIBLING and MMP expression in cementoblasts, in vitro.
Materials & Methods: Immortalized murine cementoblasts were treated with inorganic phosphate, in vitro, and effects on gene expression (by real time RT-PCR and mouse total genome microarray) were observed. Dose-response 80.1-10 mM phosphate) and time-course (1-48hr) assays were performed. A sodium-phosphate uptake inhibitor, foscarnet, was used to better define phosphate-mediated effects on cells.
Results: Three SIBLING family members were regulated by phosphate: OPN (increased over 3000f control), DMP-1 (increased over 3,00027777701060f control), and BSP (decreased). MMP3 was dramatically increased (4,00026651125000f control), paralleling regulation of its partner OPN. Both MMP2 and MMP9 were slightly down-regulated. Time-course experiments indicated a response for SIBLING and MMP genes within 24 hr. Use of foscarnet demonstrated that phosphate uptake was required for observed changes in gene expression.
Discussion: These results indicate an effect of phosphate on cementoblast SIBLING and MMP expression in vitro. During cementum formation, phosphate may be an important regulator of cementoblast activity, including modulation of biomineralization, attachment, and matrix modification
The contribution of financial entities to the sustainable development through the reporting of corporate social responsibility information
This paper aims at examining the relationship between board composition and corporate
social responsibility (CSR) of a sample of listed financial entities, discussing the driving
reasons of these entities to disclose CSR information. We hypothesize that there is a positive
association between outside (institutional and independent directors) and female directors and
CSR disclosure and a negative relationship between inside directors and CSR reporting. Our
findings provide evidence that the proportions of independent directors and female directors
on boards encourage CSR disclosure. Moreover, the results also show that the proportions of
inside directors and institutional directors on boards do not have influence on CSR reporting.
Thus, our evidence suggests that board attributes such as independent and female directors
encourage financial entities to report CSR matters, showing the effectiveness of these two
corporate governance mechanisms. The paper shed light on the influence of board structure of
financial entities on CSR disclosure. Therefore, this study contributes to past research by
providing an index to measure CSR disclosure of financial entities and the importance of the
distinction between outside and inside directors
5-hydroxymethyl-cytosine enrichment of non-committed cells is not a universal feature of vertebrate development
5-hydroxymethyl-cytosine (5-hmc) is a cytosine modification that is relatively abundant in mammalian pre-implantation
embryos and embryonic stem cells (Esc) derived from mammalian blastocysts. Recent observations imply that both
5-hmc and Tet1/2/3 proteins, catalyzing the conversion of 5-methyl-cytosine to 5-hmc, may play an important role in
self renewal and differentiation of Escs. here we assessed the distribution of 5-hmc in zebrafish and chick embryos
and found that, unlike in mammals, 5-hmc is immunochemically undetectable in these systems before the onset of
organogenesis. In addition, Tet1/2/3 transcripts are either low or undetectable at corresponding stages of zebrafish
development. however, 5-hmc is enriched in later zebrafish and chick embryos and exhibits tissue-specific distribution in adult zebrafish. Our findings show that 5-hmc enrichment of non-committed cells is not a universal feature of vertebrate development and give insights both into evolution of embryonic pluripotency and the potential role of 5-hmc in its regulation
Atomic Force Mechanobiology of Pluripotent Stem Cell-Derived Cardiomyocytes
We describe a method using atomic force microscopy (AFM) to quantify the mechanobiological properties of pluripotent, stem cell-derived cardiomyocytes, including contraction force, rate, duration, and cellular elasticity. We measured beats from cardiomyocytes derived from induced pluripotent stem cells of healthy subjects and those with dilated cardiomyopathy, and from embryonic stem cell lines. We found that our AFM method could quantitate beat forces of single cells and clusters of cardiomyocytes. We demonstrate the dose-responsive, inotropic effect of norepinephrine and beta-adrenergic blockade of metoprolol. Cardiomyocytes derived from subjects with dilated cardiomyopathy showed decreased force and decreased cellular elasticity compared to controls. This AFM-based method can serve as a screening tool for the development of cardiac-active pharmacological agents, or as a platform for studying cardiomyocyte biology
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INSPIRE: A European training network to foster research and training in cardiovascular safety pharmacology
Safety pharmacology is an essential part of drug development aiming to identify, evaluate and investigate undesirable pharmacodynamic properties of a drug primarily prior to clinical trials. In particular, cardiovascular adverse drug reactions (ADR) have halted many drug development programs. Safety pharmacology has successfully implemented a screening strategy to detect cardiovascular liabilities, but there is room for further refinement. In this setting, we present the INSPIRE project, a European Training Network in safety pharmacology for Early Stage Researchers (ESRs), funded by the European Commission's H2020-MSCA-ITN programme. INSPIRE has recruited 15 ESR fellows that will conduct an individual PhD-research project for a period of 36 months. INSPIRE aims to be complementary to ongoing research initiatives. With this as a goal, an inventory of collaborative research initiatives in safety pharmacology was created and the ESR projects have been designed to be complementary to this roadmap. Overall, INSPIRE aims to improve cardiovascular safety evaluation, either by investigating technological innovations or by adding mechanistic insight in emerging safety concerns, as observed in the field of cardio-oncology. Finally, in addition to its hands-on research pillar, INSPIRE will organize a number of summer schools and workshops that will be open to the wider community as well. In summary, INSPIRE aims to foster both research and training in safety pharmacology and hopes to inspire the future generation of safety scientists
The internal thoracic artery skeletonization study: A paired, within-patient comparison [NCT00265499]
BACKGROUND: Traditional harvesting of the internal thoracic artery (ITA) for use as a conduit in coronary bypass surgery involves the dissection of a rim of tissue surrounding the artery on either side. Recent studies, primarily observational, have suggested that skeletonization of the ITA can improve conduit flow, increase length, and reduce the risk of deep sternal infection in high risk patients. Furthermore, skeletonization of the ITA can potentially preserve intercostal nerves and reduce post-operative pain and dysesthesias associated with ITA harvesting. In order to assess the effects of ITA skeletonization, we report a prospective, randomized, within-patient study design that shares many features of a cross-over study. METHODS: Patients undergoing bilateral internal thoracic artery harvest will be randomized to having one side skeletonized and the other harvested in a non-skeletonized manner. Outcome measures include ITA flow and length measured intra-operatively, post-operative pain and dysesthesia, evaluated at discharge, four weeks, and three months post-operatively, and sternal perfusion assessed using single photon emission computed tomography. Harvest times as well as safety endpoints of ITA injury will be recorded. DISCUSSION: This study design, using within-patient comparisons and paired analyses, minimizes the variability of the outcome measures, which is seldom possible in the evaluation of surgical techniques, with minimal chance of carryover effects that can hamper the interpretation of traditional cross-over studies. This study will provide a valid evaluation of clinically relevant effects of internal thoracic artery skeletonization in improving outcomes following coronary artery bypass surgery
Effects of cardioactive drugs on human induced pluripotent stem cell derived long QT syndrome cardiomyocytes
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