Publications by authors named "Dimitrios Kalpaxis"

Article Synopsis
  • The study investigates how trace metals in seawater affect oxidative stress and protein synthesis in mussels.
  • Mussels were exposed to copper, mercury, or cadmium over two different time periods, and oxidative damage was assessed through specific biomarkers.
  • Results indicated that cadmium caused the most significant oxidative damage, though some effects diminished after prolonged exposure, suggesting potential applications in tracking marine pollution.
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Background: The os trigonum (OT)-the most common accessory bone of the foot-although usually asymptomatic, may cause posterior ankle impingement syndrome (PAIS), which may be a severely debilitating problem for recreational or competitive athletes. The aim of the present study was to evaluate effectiveness of posterior ankle arthroscopy and to assess the outcome in the treatment of PAIS secondary to OT impingement or OT fractures within a group of young athletes and their return to previous sports level.

Methods: From 2011 to 2018, a retrospective review of 81 recreational athletes of mean age 27.

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Over the last years, we have been focused on chloramphenicol conjugates that combine in their structure chloramphenicol base with natural polyamines, spermine, spermidine and putrescine, and their modifications. Conjugate , with spermidine (SPD) as a natural polyamine linked to chloramphenicol base, showed the best antibacterial and anticancer properties. Using as a prototype, we here explored the influence of the antibacterial and anticancer activity of additional benzyl groups on N1 amino moiety together with modifications of the alkyl length of the aminobutyl fragment of SPD.

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Numerous studies have shown the ability of trace metals to accumulate in marine organisms and cause oxidative stress that leads to perturbations in many important intracellular processes, including protein synthesis. This study is mainly focused on the exploration of structural changes, like base modifications, scissions, and conformational changes, caused in 18S and 5S ribosomal RNA (rRNA) isolated from the mussel Mytilus galloprovincialis exposed to 40μg/L Cu, 30μg/L Hg, or 100μg/L Cd, for 5 or 15days. 18S rRNA and 5S rRNA are components of the small and large ribosomal subunit, respectively, found in complex with ribosomal proteins, translation factors and other auxiliary components (metal ions, toxins etc).

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Article Synopsis
  • Chloramphenicol (CAM) is a bacteriostatic antibiotic that inhibits bacterial protein synthesis and has specific effectiveness against bacteria causing meningitis.
  • While it has some bactericidal properties, resistance and side effects like neurotoxicity and hematologic disorders limit its use in clinical settings.
  • The review discusses past and current efforts to develop CAM derivatives with better pharmacological properties and their potential roles in studying the ribosomal catalytic center.
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Article Synopsis
  • The study focuses on improving chloramphenicol (CAM), an older antibiotic that has seen reduced use due to side effects and resistance issues, by creating modified dimer versions to enhance its effectiveness.
  • Several CAM-dimers were synthesized and tested, with one particular compound, dubbed compound 5, showing significantly improved binding and bacteriostatic action compared to standard CAM.
  • Compound 5 demonstrated effectiveness against both resistant and non-resistant bacterial strains, and also showed potential for use in targeting T-leukemic cells while not harming normal human lymphocytes.
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A series of chloramphenicol (CAM) amides with polyamines (PAs), suitable for structure-activity relationship studies, were synthesized either by direct attachment of the PA chain on the 2-aminopropane-1,3-diol backbone of CAM, previously oxidized selectively at its primary hydroxyl group, or from chloramphenicol base (CLB) through acylation with succinic or phthalic anhydride and finally coupling with a PA. Conjugates 4 and 5, in which the CLB moiety was attached on N4 and N1 positions, respectively, of the N(8),N(8)-dibenzylated spermidine through the succinate linker, were the most potent antibacterial agents. Both conjugates were internalized into Escherichia coli cells by using the spermidine-preferential uptake system and caused decrease in protein and polyamine content of the cells.

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Ketolides belong to the latest generation of macrolides and are not only effective against macrolide susceptible bacterial strains but also against some macrolide resistant strains. Here we present data providing insights into the mechanism of action of K-1602, a novel alkyl-aryl-bearing fluoroketolide. According to our data, the K-1602 interacts with the ribosome as a one-step slow binding inhibitor, displaying an association rate constant equal to 0.

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Background And Purpose: The urothelium represents "the tightest and most impermeable barrier in the body." We investigated the distribution of paclitaxel (PTX) in the ureteral wall after the inflation of a paclitaxel-eluting balloon (PEB) in an attempt to elucidate the possibility of clinical application of PEBs in the ureter.

Materials And Methods: Nine domestic pigs were used.

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Article Synopsis
  • Chloramphenicol (CAM) is a broad-spectrum antibiotic with potential toxicity, limiting its use in developed countries.
  • A new series of polyamine-CAM conjugates were created to enhance drug uptake and effectiveness, with specific structural modifications contributing to improved antibacterial and anticancer activities.
  • Two of these compounds (4 and 5) showed superior performance against bacterial infections and demonstrated safer toxicity profiles for human cancer cells compared to CAM.
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Polyamines, in particular spermidine and spermine, have been identified as important antioxidants, highly induced by oxidative stress in a variety of organisms. However, little is known about changes in polyamine content of metal-stressed marine organisms. In the present study, mussels (Mytilus galloprovincialis) were experimentally exposed to 25 μg/L Cd(2+) or 100 μg/L Cd(2+) for up to 15 days.

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Ketolides, the third generation of expanded-spectrum macrolides, have in the last years become a successful weapon in the endless war against macrolide-resistant pathogens. Ketolides are semisynthetic derivatives of the naturally produced macrolide erythromycin, displaying not only improved activity against some erythromycin-resistant strains but also increased bactericidal activity as well as inhibitory effects at lower drug concentrations. In this study, we present a series of novel ketolides carrying alkyl-aryl side chains at the C-6 position of the lactone ring and, additionally, one or two fluorine atoms attached either directly to the lactone ring at the C-2 position or indirectly via the C-13 position.

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The ribosomal exit tunnel had recently become the centre of many functional and structural studies. Accumulated evidence indicates that the tunnel is not simply a passive conduit for the nascent chain, but a rather functionally important compartment where nascent peptide sequences can interact with the ribosome to signal translation to slow down or even stop. To explore further this interaction, we have synthesized short peptides attached to the amino group of a chloramphenicol (CAM) base, such that when bound to the ribosome these compounds mimic a nascent peptidyl-tRNA chain bound to the A-site of the peptidyltransferase center (PTC).

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Mercury is an element naturally occurring in the biosphere, but is also released into the environment by human activities, such as mining, smelting, and industrial discharge. Mercury is a biologically harmful element and any exposure of living organisms mainly due to contamination, can cause severe or even lethal side effects. In every form detected, elemental, inorganic, or organic, mercury exhibits toxicity associated with induced oxidative stress.

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Article Synopsis
  • Telithromycin binds to E. coli ribosomes in a two-step process: first at a low-affinity site and then moves to a high-affinity site.
  • The initial binding involves the lactone ring positioned near the peptide exit tunnel, while the alkyl-aryl side chain interacts with specific rRNA nucleotides.
  • Mutations affecting key nucleotide interactions impact the binding transition to the high-affinity site, suggesting that structural changes in the ribosome play a crucial role in antibiotic effectiveness.
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Certain metals, like Hg, Cu and Cd, are capable of down-regulating protein synthesis in several marine organisms, including Mytilus galloprovincialis. Nevertheless, due to the complexity of the environmental stress, it is difficult to evaluate the influence of individual metals on protein synthesis via field studies. To bypass this difficulty, experimental studies were carried out on M.

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Ketolides are effective not only against macrolide-sensitive bacteria but also against some macrolide-resistant strains. Here we present data regarding a new ketolide with an alkyl-aryl side chain at C-13 of its lactone ring. It behaves as a strong inhibitor of protein synthesis in a model coupled transcription/translation system, although it does not affect the accuracy of translation.

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Ketolides represent the latest generation of macrolide antibiotics, displaying improved activities against some erythromycin-resistant strains, while maintaining their activity against erythromycin-susceptible ones. In this study, we present a new ketolide, K-1325, that carries an alkyl-aryl side chain at C-13 of the lactone ring. According to our genetic and biochemical studies, K-1325 binds within the nascent polypeptide exit tunnel, at a site previously described as the primary attachment site of all macrolide antibiotics.

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Azithromycin is a semisynthetic derivative of erythromycin that inhibits bacterial protein synthesis by binding within the peptide exit tunnel of the 50S ribosomal subunit. Nevertheless, there is still debate over what localization is primarily responsible for azithromycin binding and as to how many molecules of the drug actually bind per ribosome. In the present study, kinetic methods and footprinting analysis are coupled together to provide time-resolved details of the azithromycin binding process.

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Heavy metals are commonly associated with the generation of reactive oxygen species (ROS), which may cause oxidative damage to several cellular macromolecules and organelles. In an attempt to correlate biomarker responses to oxidative stress, caged mussels (Mytilus galloprovincialis) were exposed for 30 days in a relatively clean site and two areas (Stations 1 and 2) unevenly polluted by heavy metals in Gulf of Patras (Greece). Three periods of caging were: one in winter, the second in spring, and the third in autumn.

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Article Synopsis
  • Erythromycin and tylosin, two macrolide antibiotics, bind to E. coli ribosomes in a two-step process involving initial weak binding followed by a stronger interaction.
  • The binding sites differ, with tylosin transitioning to a high-affinity site more quickly than erythromycin due to specific interactions with ribosomal RNA.
  • Moreover, environmental factors like Mg2+ ions and polyamines influence how each antibiotic binds and stabilizes its complex with the ribosome, highlighting the significance of their distinct side chain interactions.
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5S rRNA is an integral component of the large ribosomal subunit in virtually all living organisms. Polyamine binding to 5S rRNA was investigated by cross-linking of N1-azidobenzamidino (ABA)-spermine to naked 5S rRNA or 50S ribosomal subunits and whole ribosomes from Escherichia coli cells. ABA-spermine cross-linking sites were kinetically measured and their positions in 5S rRNA were localized by primer extension analysis.

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In the crystal structure of the 30S ribosomal subunit from Thermus thermophilus, cysteine 24 of ribosomal protein S14 (TthS14) occupies the first position in a CXXC-X12-CXXC motif that coordinates a zinc ion. The structural and functional importance of cysteine 24, which is widely conserved from bacteria to humans, was studied by its replacement with serine and by incorporating the resulting mutant into Escherichia coli ribosomes. The capability of such modified ribosomes in binding tRNA at the P and A-sites was equal to that obtained with ribosomes incorporating wild-type TthS14.

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Protein synthesis down-regulation is a life-saving mechanism for many organisms exposed to xenobiotics that threaten normal life. The present study was designed to assess the spatial and seasonal variability of global protein synthesis, determined in the microsomal fraction of digestive glands from caged Mytilus galloprovincialis mussels exposed for 30 days in a relatively clean region and two unevenly polluted areas (Stations 1 and 2) along the Gulf of Patras (Greece). The in vivo activity of translating ribosomes was evaluated by analyzing the translating ribosomes, polysome content, which may serve as an indicator of the efficiency of the protein-synthesizing machinery.

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Article Synopsis
  • A new class of 16-membered 9-aryl-alkyl oxime derivatives of 5-O-mycaminosyl-tylonolid (OMT) shows significant effectiveness against macrolide-resistant bacterial strains.
  • These compounds do not interfere with typical ribosomal functions like tRNA binding or peptidyl transfer, but they significantly inhibit poly(A)-dependent protein synthesis.
  • They appear to bind to the ribosome in a way that blocks the classic macrolide binding site, allowing them to compete with other antibiotics and suggesting their potential as new drug candidates.
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