1,721,366 research outputs found
Endothelium as a source and target of H2S to improve its trophism and function
The vascular endothelium consists of a single layer of squamous endothelial cells (ECs) lining the inner surface of blood vessels. Nowadays, it is no longer considered as a simple barrier between the blood and vessel wall, but a central hub to control blood flow homeostasis and fulfill tissue metabolic demands by furnishing oxygen and nutrients. The endothelium regulates the proper functioning of vessels and microcirculation, in terms of tone control, blood fluidity, and fine tuning of inflammatory and redox reactions within the vessel wall and in surrounding tissues. This multiplicity of effects is due to the ability of ECs to produce, process, and release key modulators. Among these, gasotransmitters such as nitric oxide (NO) and hydrogen sulfide (H2S) are very active molecules constitutively produced by endotheliocytes for the maintenance and control of vascular physiological functions, while their impairment is responsible for endothelial dysfunction and cardiovascular disorders such as hypertension, atherosclerosis, and impaired wound healing and vas-cularization due to diabetes, infections, and ischemia. Upregulation of H2S producing enzymes and administration of H2S donors can be considered as innovative therapeutic approaches to improve EC biology and function, to revert endothelial dysfunction or to prevent cardiovascular disease pro-gression. This review will focus on the beneficial autocrine/paracrine properties of H2S on ECs and the state of the art on H2S potentiating drugs and tools
Effect of selective tachykinin receptor antagonists on the growth of human skin fibroblasts.
The effect of synthetic selective tachykinin receptor antagonists was studied on the growth of cultured human skin fibroblasts (HF). Selective antagonists for the NK1 receptor ([D-Pro4, D-Trp7,9,Phe11]-SP(4-11), GR71251 and L 668,169) and the NK2 receptor (L 659,877) were tested against Substance P (SP), against the selective NK1 receptor agonist [beta-Ala4,Sar9, Met(O2)11]-SP(4-11) and against basic Fibroblast Growth Factor (bFGF). All the selective NK1 receptor antagonists, tested at the concentration of 10(-5)M, induced a significant displacement to the right of the dose-response curves induced by SP and by the selective NK1 receptor agonist. The selective NK2 receptor antagonist did not modify the proliferative response to the tachykinins used. The growth promoting effect of bFGF was not modified by any of the tachykinin antagonists tested. These results indicate that the newly developed receptor-selective tachykinin antagonists appear to be a useful tool to assess the biological effects of tachykinin in vitro on cultured isolated cells
Nitric oxide in tumor angiogenesis
Nitric oxide (NO), produced from L-arginine by NO synthases (NOS), is a short-lived molecule required for many physiological functions and contributing to different pathological conditions. In the last decade, we and others contributed to demonstrate that NO stimulates angiogenesis and mediates the effect of different angiogenic molecules. In human tumors, NOS expression and activity correlate with tumor growth and aggressiveness through angiogenesis stimulation and regulation of angiogenic factor expression. Interrelations among the NOS pathway, prostanoids and tyrosine kinase receptors have been reported in regulating tumor progression and malignancy. Drugs affecting the NOS pathway may be forseen as anti-tumor strategies able to reduce edema, inhibit angiogenesis and facilitate the delivery of chemotherapeutical agents. Recent developments include research on NOS gene polymorphisms which might become useful biomarkers for predicting cancer susceptibility as well as the role of NO in chemopreventive strategies. © 2008 Springer US
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
The sulphydryl containing ACE inhibitor Zofenoprilat protects coronary endothelium from Doxorubicin-induced apoptosis
Pediatric and adult cancer patients, following the use of the antitumor drug Doxorubicin develop cardiotoxicity. Pharmacological protection of microvascular endothelium might produce a double benefit: (i) reduction of myocardial toxicity (the primary target of Doxorubicin action) and (ii) maintenance of the vascular functionality for the adequate delivery of chemotherapeutics to tumor cells. This study was aimed to evaluate the mechanisms responsible of the protective effects of the angiotensin converting enzyme inhibitor (ACEI) Zofenoprilat against the toxic effects exerted by Doxorubicin on coronary microvascular endothelium. We found that exposure of endothelial cells to Doxorubicin (0.1-1μM range) impaired cell survival by promoting their apoptosis. ERK1/2 related p53 activation, but not reactive oxygen species, was responsible for Doxorubicin induced caspase-3 cleavage. P53 mediated-apoptosis and impairment of survival were reverted by treatment with Zofenoprilat. The previously described PI-3K/eNOS/endogenous fibroblast growth factor signaling was not involved in the protective effect, which, instead, could be ascribed to cystathionine gamma lyase dependent availability of H2S from Zofenoprilat. Furthermore, considering the tumor environment, the treatment of endothelial/tumor co-cultures with Zofenoprilat did not affect the antitumor efficacy of Doxorubicin. In conclusion the ACEI Zofenoprilat exerts a protective effect on Doxorubicin induced endothelial damage, without affecting its antitumor efficacy. Thus, sulfhydryl containing ACEI may be a useful therapy for Doxorubicin-induced cardiotoxicity
Nitric oxide modulates the angiogenic phenotype of middle-T transformed endothelial cells.
The role of nitric oxide (NO) in the induction of angiogenesis was evaluated in a murine heart endothelioma cell line (H.end.FB) carrying the mT oncogene. Two clonal derivatives of H.end.FB, H80 and H73, exhibiting different NO synthase (NOS) activities were selected and used in the study. The relationship among NOS activity and tumor cell behaviour (growth, and angiogenic capacity) and the molecular control of gene expression were investigated. H.end.FB and H80 on one side and H73 on the other side exhibited the highest and lowest NOS activity, respectively. Cell growth was inversely correlated to the amount of NO produced by the cell lines. Conversely, in the avascular rabbit cornea assay, H.end.FB and H80 cells were strongly angiogenic, while H73 were poorly angiogenic, indicating that the ability of the cells to induce neovascularization was associated with the extent of NO produced. Consistently, systemic administration to rabbits of the NOS inhibitor N(w)-nitro-L-arginine methyl ester (L-NAME) significantly reduced the angiogenicity of H.end.FB cells. RT-PCR evidenced that H.end.FB expressed mRNA for TGF-beta1 and all VEGF isoforms, VEGF165 being predominantly expressed. NOS inhibition reduced the basal expression of VEGF isoforms, while it markedly potentiated TGF-beta1 expression. These results indicate that the endogenous production of NO in tumor cells can serve as an autocrine/paracrine signalling mechanism of progression, by controlling angiogenic factor/modulator expressio
Variations on the Author
“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
A nanoscale fluorocarbon coating on PET improves the adhesion and growth of cultured coronary endothelial cells
Plasma deposition was applied to deposit smooth and nanostructured fluorocarbon coatings on polyethylene terephthalate substrates, with the aim to obtain surfaces with identical chemical
composition but different roughness to improve the endothelialization process on PET surfaces.
We found that increased roughness was associated with enhanced endothelial cell response, as shown by the ability of cells to grow and adhere to nanostructures. We also observed specific
interaction of filopodia protruding from the cell membrane with individual nanostructures, leading to increased cell attachment, spreading and cell viability. Among the modified surfaces, one termed PET-tfl90 emerged as the one capable of best sustaining the formation of a confluent monolayer of endothelial cells.
In conclusion, PET modified by nanostructured fluorocarbon film represents an improved graft material, over conventional PET, for endothelial cell adhesion and growth
Appropriate Similarity Measures for Author Cocitation Analysis
We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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