1,721,059 research outputs found
Calcification onset/progression correlates with phospholipid intracellular accumulation/rearrangement in mineralizing aortic valves
No full textDegenerative calcification occurring in failing heart bioprosthetic valves is still poorly understood. In "in vivo" calcification models, mineralization onset takes place at level of cells (1) or cell nuclei (2). In porcine aortic valves subdermally implanted in rat subcutis for 6 weeks, we found that calcification correlates with the presence of peculiar acidic phospholipid layers (PPLs) surrounding cells and matrix vesicles (3-5). Here, we investigated valve mineralization after shorter implantation times to understand how PPLs form and correlate with mineralization progress. Chemical analyses revealed initial calcium deposition before 2-day-long implantation and its linear increase with time. Ultrastructural observations revealed lipid accumulation within more and more numerous vacuoles filling cell cytoplasm in 2-day and and 1-week implanted valves. Initial PPL formation was observed in 1-week implanted valves, whereas PPLs involved most cells after longer implantation times. These data suggest that (a) direct correlation does exist between calcification rate and acidic phospholipid accumulation and (b) PPL genesis is due to distinct intracellular modifications which seem to depend on a peculiar pattern of phospholipidosis. (1) Schoen FJ, Levy RJ, Nelson AC et al. Lab Invest, 5: 523-532; 1985. (2) Girardot MN, Torrianni M, Dillehay D et al. , 29: 793-801; 1995. (3) Ortolani F, Petrelli L, Tubaro F et al. Connect Tiss Res, 43: 44-55; 2002. (4) Ortolani F, Tubaro F, Petrelli L et al. Histochem J, 34: 41-50; 2002. (5) Ortolani F, Petrelli L, Nori SL et al. Histol Histopathol, in press; 2003
Elastin and collagen interact with cell-derived acidic phospholipid membranes in the progression of mineralization in calcifying aortic valves
No full textINTRODUCTION Elastin fibers have been reported to be prone to mineralization in ageing and in a number of cardiovascular diseases including bioprosthetic valve calcification. Different mechanisms seem to exist which direct these mineralization processes such as in aorta atherosclerotic plaques, where calcification is preceded by accumulation of cholesterol esters and neutral lipids inside altered elastin fibers [1], or that in subdermally implanted aorta wall segments, where calcification occurs at the outer aspect of elastin fibers interacting with undefined amorphous material [2]. Recently, we found that fixation/reactions with glutaraldehyde and cationic copper-phthalocyanine Cuprolinic blue (GACB) at low salt-critical-electrolyte-concentration and pH were suitable for studying calcification in subdermally implanted aortic valves, because of tissue unmasking form mineral and simultaneous visualization at the ultrastructural level of unique, electrondense layers outlining calcifying cells and matrix-vesicle-like structures [3,4]. The observed reactivity and susceptibility to extraction with chloroform-methanol suggested these pericellular layers to be formed by acidic phospholipids which will cluster at cell surfaces replacing cell plasma membranes. Here, a modified glutaraldehyde-malachite-green method (GA-MG) was used to support the concept of lipid involvement in valve calcification and to assess how elastin fibers and collagen fibrils are involved in the mineralization progression from the cells into the extracellular matrix. MATERIAL AND METHODS Animal model inducing calcification: 6-week long implantation of porcine aortic valve leaflets in rat subcutis [5]. Processing of explanted samples: (A) immersion in 25mM sodium acetate buffer, containing 0.05% Cuprolinic blue + 0.05M MgCl2 + 2,5% glutaraldehyde, pH 4.8, at room temperature for 4 days (GACB); (B) immersion in 0.067 mol/L cacodylate buffer solution, containing 3% glutaraldehyde and 0.1% Malachite green, pH 4.8, at 4°C for 18h (GAMG). Post-fixation in 2% OsO4 in phosphate buffer, pH 7.2; dehydration in graded ethanols; embedding in Araldite/Epon. (A-C) thin section staining with uranyl acetate and lead citrate. RESULTS On thin sections, GAMG-subjected samples showed reactivity patterns superimposable to those observed for GACB-treated samples. Namely, decalcifying effect occurred with associated unmasking of cells and matrix vesicles, which appeared to be outlined by MG-reactive, electrondense borders (Fig.1). In addition, mineralization spreading from cells to adjacent extracellular matrix was characterized by outward growing of the MG-reactive material, which enveloped electron-lucent elastin fibers and collagen fibrils, and the additional presence of amorphous material embedding all these components (Fig.2). Despite demineralization, calcium precipitates were observed to be retained by most elastin fibers interacting with MG-reactive material , whereas no mineral deposits was found either on iuxta-cellular fibers still not involved in such a relationship, or those lying in uncalcified extracellular matrix. DISCUSSION GA-MG method reveals acidic phospholipid distribution because it allows lipid retention in the sample, with subsequent formation of electron-dense GA-MG-OsO4-lipid complexes during standard post-fixation with osmium tetroxyde [6]. The lower pH here used allowed to obtain tissue demineralization with preservation of proper reactivness. In the experimental conditions adopted, acidic phospholipids appeared to be accumulated at cell and matrix vesicle surfaces, i.e. where primary calcification occurs, and to be also involved in subsequent mineralization progression into the ECM. Here, elastic fibers and collagen fibrils seem to require prior surface interaction with cell-derived acidic phospholipids before undergoing mineralization, in agreement with the concept that their calcification need interaction with additional molecules [1,3] and/or cell degradation products [3,7]. The concept is supported that elastin fibers can undergo calcification according to different mechanisms which include intrinsic alterations as well as interaction with polyanionic molecules such as proteoglycans, as suggested for pseudoxanthoma elasticum [8], or acidic phospholipids, as suggested by the present data. ACKNOWLEDGEMENTS This work was supported by a special grant by Cassa di Risparmio di Padova e Rovigo Foundation. REFERENCES [1] Bobryshev YV, Lord RS. Atherosclerosis 42, 197-198 (1999). [2] Paule WJ, Bernick S, Strates B, Nimni ME. J. Biomed. Mater. Res. 26, 1169-1177 (1992). [3] Ortolani F, Petrelli L, Tubaro F, Spina M, Marchini M. Connect. Tiss. Res. 43, 44-55 (2002). [4] Ortolani F, Tubaro F, Petrelli L, Gandaglia A, Spina M, Marchini M. Histochem. J. 34, 41-50 (2002). [5] Schoen FJ, Tsao JW, Levy RJ. Am. J. Pathol. 123, 134-145(1986). [6] Bonucci E, Silvestrini G. Bone 15, 153-160 (1994). [7] Kim KM. Scan. Electron. Microsc. 9, 1137-1175 (1995). [8] Pasquali Ronchetti I, Baccarani-Contri M, Fornieri C., Mori G., Quaglino D. jr. Micron 24, 75-89 (1993)
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Vitamin C prevents zidovudine-induced NAD(P)H oxidase activation and hypertension in the rat
No full textCardiovasc Res. 2007 Jan 15;73(2):432-8. Epub 2006 Oct 20.
Vitamin C prevents zidovudine-induced NAD(P)H oxidase activation and hypertension in the rat.
Papparella I, Ceolotto G, Berto L, Cavalli M, Bova S, Cargnelli G, Ruga E, Milanesi O, Franco L, Mazzoni M, Petrelli L, Nussdorfer GG, Semplicini A.
Source
Department of Clinical and Experimental Medicine, University of Padova, Via Giustiniani 2, I-35128 Padua, Italy.
Abstract
OBJECTIVE:
Cardiovascular risk is increased among HIV-infected patients receiving antiretroviral therapy due to the development of hypertension and metabolic abnormalities. In this study, we investigated the effects of long-term treatment with zidovudine (AZT) and vitamin C, alone and in combination, on blood pressure and on the chain of events linking oxidative stress to cardiac damage in the rat.
METHODS:
Six adult Wistar Kyoto rats received AZT (1 mg/ml) in the drinking water for 8 months, six vitamin C (10 g/kg of food) and AZT, six vitamin C alone, and six served as controls.
RESULTS:
AZT increased systolic blood pressure, expression of gp91(phox) and p47(phox) subunits of NAD(P)H oxidase, and protein kinase C (PKC) delta activation and reduced antioxidant power of plasma and cardiac homogenates. AZT also caused morphological alterations in cardiac myocyte mitochondria, indicative of functional damage. All of these effects were prevented by vitamin C.
CONCLUSION:
Chronic AZT administration increases blood pressure and promotes cardiovascular damage through a NAD(P)H oxidase-dependent mechanism that involves PKC delta. Vitamin C antagonizes these adverse effects of AZT in the cardiovascular system.
PMID:
17123493
[PubMed - indexed for MEDLINE
Variations on the Author
Full text link“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
Intracapsular microenucleation technique in a case of intraparotid facial nerve schwannoma. Technical notes for a conservative approach
No full textSummary: We report a rare case of a large intraparotid facial nerve schwannoma (IFNS) in a 51-year-old female who presented with a painless, slow growing left parotid mass without peripheral facial nerve palsy, with non-specific findings at preoperative diagnostic work-up, that was treated with conservative surgery. Management of IFNS is very challenging because the diagnosis is often made intra-operatively, and in most cases resection may lead to severe facial nerve paralysis, with important aesthetic sequelae. Our experience suggests a new surgical option, namely intra-capsular enucleation using a microscope, currently used for schwannomas arising from a major peripheral nerve, which should be a safe and reliable treatment for IFNS. This surgical technique is the first experience of intracapsular microenucleation of facial nerve schwannoma described in the literature and allows preservation of the nerve without resection and reconstruction
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe 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
Involvement of phosphodiesterase in the refractoriness of the Sertoli cell
No full textGonadotropin treatment of the Sertoli cell produces a marked refractory state of the cell to subsequent hormonal stimulation. Because FSH also stimulates the phosphodiesterase activity of these cells, the possible involvement of an altered cAMP catabolism during refractoriness was investigated in an in vitro model. Sertoli cells, after 3 days of culture in a defined medium, were exposed to FSH or isoproterenol for 1-24 h. After this pretreatment, cells were stimulated for 1 h with a maximal FSH dose, and the responsiveness was measured in terms of cAMP accumulation. Sertoli cells previously treated with hormone entered a refractory state, a second exposure being ineffective in elevating intracellular or extracellular cAMP. Addition of the phosphodiesterase inhibitor 3-isobutyl-methylxanthine in the second incubation partially restored the ability of the cell to accumulate cAMP in the presence of hormone. This phosphodiesterase inhibitor also caused an apparent decrease in the potency of FSH to induce the refractory state. Such an impairment of response developed in the intact cell in 4 h, and was accompanied by a partial desensitization of the adenylate cyclase and an increase in phosphodiesterase activity. The stimulation of phosphodiesterase activity, but not the desensitization of adenylate cyclase, was inhibited by cycloheximide. The inhibition of protein synthesis also prevented the onset of the refractory state of the intact Sertoli cell. Pretreatment of the Sertoli cells with either FSH or isoproterenol rendered the cell refractory to a second stimulation with either agonist; in contrast, the adenylate cyclase desensitization in the homogenate was apparent only for the agonist employed in the preincubation. These results indicate that phosphodiesterase regulation is involved in the control of Sertoli cell responsiveness to hormone. Thus, the net decrease in cAMP production of the FSH-treated cells is the result of a decreased adenylate cyclase stimulation and an increased cAMP catabolism mediated by phosphodiesterase. The latter phenomenon appears to be the predominant cause of the partial refractoriness induced by low doses of gonadotropin
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