1,721,051 research outputs found
A comparative study of the hemolytic effect of polyenic antibiotics and of other cholesterol-binding agents.
No full textMacrocyclic polyenic antibiotics were compared, on the basis of their hemolytic efficiency (expressed as critical occupancy level and as mean intrinsic association constant) with each other and with other cholesterol-specific hemolytic agents, such as digitonin and streptolysin O. In all cases, except for the larger polyenic antibiotics (amphotericin B and nystatin), the experimental results were compatible with the existence in the membrane of a large number of identical binding sites which are independent from each other. Simultaneous addition of two different agents gave either synergistic or antagonistic effects, indicating that digitonin, streptolysin O and filipin have different mechanisms of action from each other and from the mycosamine-containing polyenes
AZT: An old drug with new perspectives
No full textThe science of antiviral research was well advanced when HIV/AIDS appeared as a major new virus disease in
the early 1980s. The first effective antiviral compound (AZT, azidothymidine, zidovudine) was already among the library
of compounds screened and was promptly reported to be a specific inhibitor of retroviruses, including HIV. Due to the
pivotal role of AZT in HIV treatment, this review summarizes the most known effects -some of which are toxic side effects-
induced by AZT a drug which is still used in the combined therapy of HIV-infected patients. Among the toxic side
effects, a severe bone marrow toxicity manifested as anemia, neutropenia and siderosis, and caused by inhibition of heme
and globin synthesis together with a general derangement of iron supply, have been reported. In this regard, we proved
that while AZT and its monophosphorylated derivative AZTMP were unable to chelate iron, the triphosphate form
AZTTP displayed a significant capacity to remove iron from transferrin. Moreover, we have previously demonstrated that
AZT-exposed K562 cells showed an increase of transferrin receptors located on the cell membrane without affecting their
biosynthesis, but slowing down their endocytotic pathway. Interestingly, literature data report the impairement of glycosylation
reactions by AZT. Indeed, we have shown that AZT-treated K562 cells exhibited a reduced sialylation of proteins
and lipids, and a strong inhibition of alfa,(2-8) sialyltransferase activity while beta,(1-4)galactosyltransferase and beta-
galactosidase activities were significantly increased. These latter observations could be of clinical relevance since alterations
of intracellular and cell surface carbohydrate expression and composition, often are associated with several diseases.
However, contrarily to previous reports by other authors on AZT as an inhibitor of plant and bacterial toxins activity, we
have demonstrated that AZT not only did not inhibit saporin toxicity, but even increased the cytotoxic activity of this
plant toxin on K562 cells. Furthermore, the review enlightens the potential utilization of AZT as a tool in proteomics since
in the recent years several genes responding to this drug have been identified in different cell lines. We have shown, for
the first time, an over-expression of two proteins (PDI-A3 and sthatmin), and a full repression of two others (HSP-60 and
SOD1) in AZT-exposed K562 cells. At present, we are investigating if the above reported alterations are a general feature
of AZT-treatment of cultured cells, or they represent a peculiar characteristic of a specific cell line. Finally, the paper reviews
a number of novel methodologies aimed at enhancing the AZT plasma levels and its bioavailability in all human
organs in order to improve its therapeutic efficacy against HIV infection. These new possibilities, namely the AZT prodrug
strategy, the AZT transdermal delivery and the targeted brain delivery, are yet not in use for humans but they are under
experimental studies
Crabrolin, a natural antibiotic peptide: structural properties
No full textA joint application of experimental and computational approaches has revealed the exceptionally high attitude of crabrolin, a 13-
residue peptide with sequence FLPLILRKIVTAL-NH2, to adopt alpha-helix conformation not only inmembrane-mimicking solvents
but also in the presence of a not negligible amount of water. Our study shows that this propensity essentially resides in the
intrinsic thermodynamic stability of alpha-helix conformation whose kinetic stability is drastically reduced in water solvent. Our
analysis suggests that this is due to two effects enhanced by water: a more local effect consisting of the demolition of intrapeptide
H-bonds, essential for the alpha-helix formation, and a bulk – electrostatic – effect favoring conformational states more
polar than alpha-helix. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd
Shunt COX-LOX and MMPs iperproduction in NIH3T3 fibroblast treated with non steroidal antiinflammatory drugs"
No full textResveratrol: a nutural polyphenol with multiple chemopreventive properties
No full textResveratrol, a naturally occurring polyphenol, shows pleiotropic health beneficial effects, including antioxidant,
anti-inflammatory, anti-aging, cardioprotective and neuroprotective activities. Due to the several protective effects
and since this compound is widely distributed in the plant kingdom, resveratrol can be envisaged as a chemopreventive/
curative agent introduced almost daily with the diet. Currently, a number of preclinical findings suggest resveratrol
as a promising nature’s weapon for cancer prevention and treatment. A remarkable progress in elucidating the
molecular mechanisms underlying anti-cancer properties of resveratrol has been achieved in the last years. Concerning the
resveratrol mechanism of action as a protective (vs. normal cells and tissues) and toxic (vs. cancer cells) compound, many
studies focus on its antioxidant capacity as well as on its ability to trigger and favor the apoptotic cascade in malignant
cells. However, a generalized mechanism of action able to explain this dual effect of resveratrol has not yet been clearly
established. In addition to these important functions, resveratrol is reported to exhibit several other biological/biochemical
protective effects on heart, circulation, brain and age-related diseases which are summarized in this Review
Inhibition of uridine incorporation into RNA in mammalian cells by agents affecting the properties of the cell membrane: chloropromazine, dipyridamole and phenylethanol
No full textFolding propensity of anoplin: A molecular dynamics study of the native peptide and four mutated isoforms
No full textAnoplin, a cationic decapeptide amide GLLKRIKTLLNH2
derived from venom sac of the solitary wasp Anoplius
samariensis has been investigated through Molecular
Dynamics. The wild-type (WT) and four isoforms
were simulated both in water and in the membranemimicking
solvent trifluoroethanol (TFE). In water all
the investigated species, found to be in rapid equilibrium
between different conformational states, can be considered
as unfolded. On the other hand, in TFE all the systems
enhance their rigidity and, in general, show a-helix
as the main folded conformation. Interestingly, a semiquantitative
thermodynamic analysis has suggested that
the folding driving force is not always the same being in
some cases (e.g., the WT Anoplin) of entropic nature and
in other cases of energetic nature. VC 2015 Wiley Periodicals,
Inc. Biopolymers 103: 692–701, 2015
Monitoring by cis-parinaric fluorescence of free radicals induced lipid peroxidation in aqueous liposome suspensions
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