1,720,963 research outputs found
Minocycline attenuates gentamicin induced hair cell loss in neonatal cochlear cultures.
No full textMinocycline, a second-generation tetracycline antibiotic used against gram-negative and gram-positive bacteria, protects against a wide range of neurodegenerative disorders by inhibiting caspases, iNOS and the release of cytochrome c. Since aminoglycoside antibiotics damage sensory hair cells in the inner ear by activating caspase-mediated cell death pathways, we hypothesized that minocycline would protect against gentamicin (GM) ototoxicity. To test this hypothesis, postnatal day 3 (P3) rat, cochlear organotypic cultures were treated with GM alone or in combination with minocycline (10-500 microM). Treatment with GM induced a dose-dependent loss of outer hair cells (OHC) and inner hair cells (IHC). Addition of minocycline to the GM-treated cultures greatly reduced the amount of GM-induced hair cell damage in P3 cochlear cultures. The greatest protection was achieved with 100 microM of minocycline. Application of minocycline alone had no adverse effects on hair cell survival. The advantage of this combination therapy is that minocycline prevents GM-induced hair cell loss while helping to suppress the bacterial infection
MDL 28170 attenuates gentamicin Ototoxicity
No full textAminoglycosides are highly effective antibiotics; however, their clinical utility is severely limited by their nephrotoxic and ototoxic side-effects. The selective destruction of hair cells in the inner ear by aminoglycoside antibiotics is thought to arise from a carefully orchestrated programme of cell death involving caspases and calcium activated proteases or calpains. To more fully evaluate the role of calpains in aminoglycoside ototoxicity, we applied the cell permeant, selective calpain inhibitor MDL 28170, to gentamicin (GM) treated cochlear organotypic cultures and evaluated the degree of hair cell damage at various drug concentrations. Mean hair cell losses in cochlear cultures treated for 24hours with 250, 500 and 1000 μM of GM were 17, 64 and 81%, respectively. Cochlear cultures treated with 200 μM of MDL 28170 alone for 24hours had no adverse effects on hair cell survival. However, the two highest doses of MDL 28170 (500 and 1000 μM) resulted in disorganization of hair cell rows, stereocilia damage and 30–35% hair cell loss. Addition of MDL 28170 to cochlear cultures treated with 500 and 1000 μM GM enhanced hair cell survival in a dose-dependent manner. Two hundred μM of MDL 28170, which by itself had no adverse effects on hair cells survival, significantly enhanced hair cell survival (30–35%), but failed to provide complete protection against GM ototoxicity. Since MDL 28170 can cross the blood-brain barrier and prevent neurodegeneration, it could conceivably be used in vivo to attenuate aminoglycoside ototoxicity
Cisplatin-induced apoptosis in human promyelocytic leukemia cells
No full textCis-diamminedichloroplatinum (II) cisplatin (CDDP) is an
organometallic compound frequently used in anti-cancer therapy, in
particular ovarian, testicular, and head and neck tumors. We found
cisplatin was effective against human promyelocytic leukemia cell
line HL-60, inhibiting cell cycle progression and inducing time- and
concentration- dependent cell death. Presence of nuclear
fragmentation, caspase-3 cleavage and annexin V positivity suggests
cell death occurred by apoptosis, although DNA internucleosomal
fragmentation was not detected. In addition, analysis of
malondialdehyde (MDA) production and protein carbonylation indicated
that cisplatin increased lipid peroxidation and oxidation of cell
proteins. This occurrence was prevented by antioxidants such as
N-acetylcysteine (N-aC) and glutathione (GSH), which, consistently,
were also able to prevent CDDP-induced cell death. Collectively,
these findings indicate that, besides growth inhibition, an increase
of oxygen radicals and lipid degradation can account for a
significant part of CDDP-induced apoptosis
Ethanolic extract from Hemidesmus indicus (Linn) displays otoprotectant activities on organotypic cultures without interfering on gentamicin uptake
No full textThe ethanolic extract from Hemidesmus indicus (Linn) (Apocynaceae) (Hie) was studied for its otoprotective effects in ex vivo rat organotypic model of gentamicin (GM) toxicity. In organ of Corti organotypic cultures (OC), GM can induce a fast dose-dependent apoptosis of hair cells (HC), both external and internal. We found that, after coadministration of GM and Hie to organotypic cultures, the extract was able to significantly counteract this toxic effect on HC, at the concentration of 25 and 50microg/ml. Interestingly, at these concentrations the extract was present in the cell medium at a concentration 1.6- and 3.3-fold lower than GM, suggesting its otoprotective activity could not merely due to an aspecific inhibition of GM entry. To support this hypothesis, we evaluated the amount of GM present in organotypic cultures after the coadministration of 1.5mg/ml GM and Hie, and found no significant reduction of GM uptake in the presence of 100microg/ml Hie. These data suggest the otoprotective action of Hie derives from specific inhibition of the apoptotic routine induced by GM treatment
Protective effects of minocycline and MDL 28170 in gentamicin ototoxicity
No full textGentamicin side-effects on cochlear structures and function are well known, but not the detailed intracellular molecular
mechanisms which lead to aminoglycoside induced ototoxicity. Hair cell death occurs by apoptosis, by the activation of
enzymatic cascades known to be involved in the programmed cell death, or by the release of cytochrome-c from the
damaged mitochondria. In this paper we have investigated the active role of minocycline, a second-generation tetracycline,
and of MDL 28170, a selective calpain inhibitor, in the protection of hair cells from GM damage in in vitro organospecific
cultures of the organ of Corti. We used cultures from neonatal (P3) rat cochlea, treated with different dosages of GM, alone,
or with the two protector drugs. We have observed a dose-dependent OHC and IHC loss. The GM damage was reduced
after treatment with both drugs. These results were also supported by the Disk Diffusion Susceptibility Test (Kirby-Bauer
Method), in which we used drug treated organs of Corti. The data suggest that minocycline, previously reported to inhibit
the release of cytochrome-c, and MDL 28170, prevent GM induced programmed cell death pathway in cochlear HC
Gentamicin-induced cytotoxicity involves protein kinase C activation, glutathione extrusion and malondialdehyde production in an immortalized cell line from the organ of corti
No full textThe objective of the present study was to investigate the biochemical mechanisms underlying gentamicin cytotoxicity in OC-k3 cells derived from an immortalized cell line developed from the organ of Corti of transgenic mice. Administration of 50 microM gentamicin significantly reduced cell proliferation and viability, as well as initiating morphological changes associated with apoptosis. Protein kinase C (PKC) alpha activity was increased in gentamicin-treated cells, peaking 15 min after dosing (+138.2%). This PKCalpha increase was followed by a rise of glutathione (GSH) efflux and a concomitant 29% decrease in intracellular GSH levels at 30 min. PKCalpha-specific inhibitors blocked these cytotoxic effects. Gentamicin also increased malondialdehyde levels, while N-acetylcysteine, GSH and ascorbic acid prevented gentamicin-induced cell death. These findings suggest that gentamicin cytotoxicity involves a production of intracellular reactive oxygen species and a concomitant PKC-dependent fall of intracellular scavenging abilities (GSH), events that together drive cells to undergo apoptosis
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
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
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
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