Recent Biophysical Issues About the Preparation of Solute-Filled Lipid Vesicles

Here we report some recent biophysical issues on the preparation of solute-filled lipid vesicles and their relevance to the construction of “synthetic cells.” First, we introduce the “semi-synthetic minimal cells” as the liposome-based cell-like systems, which contain a minimal number of biomolecules required to display simple and complex biological functions. Next, we focus on recent aspects related to the construction of synthetic cells. Emphasis is given to the interplay between the methods of synthetic cell preparation and the physics of solute encapsulation. We briefly introduce the notion of structural and compositional “diversity” in synthetic cell populations.     

Synthesis and Evaluation of Voltage-Gated Sodium Channel Blocking Pyrroline Derivatives Endowed with Both Antiarrhythmic and Antioxidant Activities

Under the hypothesis that cardioprotective agents might benefit from synergism between antiarrhythmic activity and antioxidant properties, a small series of mexiletine analogues were coupled with the 2,2,5,5-tetramethylpyrroline moiety, known for its antioxidant effect, in order to obtain dual-acting drugs potentially useful in the protection of the heart against post-ischemic reperfusion injury. The pyrroline derivatives reported herein were found to be more potent as antiarrhythmic agents than mexiletine and displayed antioxidant activity. The most interesting tetramethylpyrroline congener, a tert-butyl-substituted analogue, was at least 100 times more active as an antiarrhythmic than mexiletine.     

Ion Channels in Multiple Myeloma: Pathogenic Role and Therapeutic Perspectives

Ion channels are pore-forming proteins that allow ions to flow across plasma membranes and intracellular organelles in both excitable and non-excitable cells. They are involved in the regulation of several biological processes (i.e., proliferation, cell volume and shape, differentiation, migration, and apoptosis). Recently, the aberrant expression of ion channels has emerged as an important step of malignant transformation, tumor progression, and drug resistance, leading to the idea of “onco-channelopathy”. Here, we review the contribution of ion channels and transporters in multiple myeloma (MM), a hematological neoplasia characterized by the expansion of tumor plasma cells (MM cells) in the bone marrow (BM). Deregulation of ion channels sustains MM progression by modulating intracellular pathways that promote MM cells’ survival, proliferation, and drug resistance. Finally, we focus on the promising role of ion channels as therapeutic targets for the treatment of MM patients in a combination strategy with currently used anti-MM drugs to improve their cytotoxic activity and reduce adverse effects.     

Novel rifamycins. I-Synthesis and antibacterial activity of 3-hydrazinorifamycin derivatives

A number of semisynthetic rifamycin derivatives, modified at position 3, belonging to general structures (II), (III), (IV), (V), (VI), (VII) and (VIII) (see Scheme), have been prepared. The synthesis, structure, and antimicrobial evaluation of the new compounds are described. All the derivatives have in vitro antibacterial activities comparable with that of rifampicin.     

First data from the EGLE experiment onboard the ISS

EGLE is a wide frequency band search- coil magnetometer designed and built at the Roma Tre University. It has been installed onboard the ISS by the Italian astronaut Roberto Vittori on April 25, 2005 within the LAZIO- EGLE experiment carried out during the ENEIDE Soyuz mission. The scope of the experiment is to test EGLE in space and to investigate geomagnetic field variations. The main applications of EGLE are the study of electromagnetic environment inside the ISS, the correlation of magnetic field data with particle fluxes detected by LAZIO particle detector, and the monitoring of ionospheric perturbations possibly caused by Earth seismic activity. Since continuous electromagnetic field measurements on board the ISS are important for diverse space applications, a magnetometer with a suitable design is requested. Appropriate solutions for these applications, which have been adopted by EGLE, are in particular the use of 1- Wire technology and the possibility to detect by means of a search- coil magnetometer a large portion of the ULF frequency band, usually measured by flux- gate probes. To investigate the topside ionosphere electromagnetic environment and stability of Van Allen radiation belts in relation with seismic and anthropogenic electromagnetic emissions, a specific satellite mission (the ESPERIA project) has been designed for the Italian Space Agency (ASI), and up to now a few instruments of its payload have been built and tested in space. One of them is exactly the EGLE search- coil magnetometer. The first magnetic observations performed by this instrument reveal to be promising and demand for a further and deeper analysis based on a longer time series of data.     

Modulation on C‐ and N‐Terminal Moieties of a Series of Potent and Selective Linear Tachykinin NK2 Receptor Antagonists

Herein we describe the synthesis of a series of new potent tachykinin NK₂ receptor antagonists by the modulation of the C‐ and N‐terminal moieties of ibodutant (MEN 15596, 1 ). The N‐terminal benzo[b]thiophene ring was replaced by different substituted naphthalenes and benzofurans, while further modifications were evaluated at the C‐terminal tetrahydropyran moiety. Most compounds demonstrated a high affinity for the human NK₂ receptor and high in vitro antagonist potency, indicating that a wide range of substituents at both termini can be incorporated in the molecule without detrimental effects on the interactions with the NK₂ receptor. Selected compounds were tested in vivo confirming their activity as NK₂ antagonists. In particular, after both iv and id administration to guinea pig, compound 61 b was able to antagonize NK₂‐induced colonic contractions with a potency and duration‐of‐action fully comparable to the reference compound 1 (MEN 15596, ibodutant).     

Enhanced inflammatory response to coronary angioplasty in patients with severe unstable angina

BACKGROUND: Systemic markers of inflammation have been found in unstable angina. Disruption of culprit coronary stenoses may cause a greater inflammatory response in patients with unstable than those with stable angina. We assessed the time course of C-reactive protein (CRP), serum amyloid A protein (SAA), and interleukin-6 (IL-6) after single-vessel PTCA in 30 patients with stable and 56 patients with unstable angina (protocol A). We also studied 12 patients with stable and 15 with unstable angina after diagnostic coronary angiography (protocol B). METHODS AND RESULTS: Peripheral blood samples were taken before and 6, 24, 48, and 72 hours after PTCA or angiography. In protocol A, baseline CRP, SAA, and IL-6 levels were normal in 87% of stable and 29% of unstable patients. After PTCA, CRP, SAA, and IL-6 did not change in stable patients and unstable patients with normal baseline levels but increased in unstable patients with raised baseline levels (all P<0.001). In protocol B, CRP, SAA, and IL-6 did not change in stable angina patients after angiography but increased in unstable angina patients (all P<0.05). Baseline CRP and SAA levels correlated with their peak values after PTCA and angiography (all P<0.001). CONCLUSIONS: Our data suggest that plaque rupture per se is not the main cause of the acute-phase protein increase in unstable angina and that increased baseline levels of acute-phase proteins are a marker of the hyperresponsiveness of the inflammatory system even to small stimuli. Thus, an enhanced inflammatory response to nonspecific stimuli may be involved in the pathogenesis of unstable angina.     

Structure-activity relationship of new 2-substituted penem antibiotics

The antibacterial activities of three new penems with 4-hydroxyprolinamide, 1-prolinamide and N-methyl-N-2-propionamide substituents, respectively, in position 2 and of their stereoisomers were examined against Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Escherichia coli and Pseudomonas aeruginosa. All substitutes conferred a broad antibacterial spectrum on the penem moiety. Changes in stereoisomerism selectively improved the activity against E. coli, S. aureus or enterococci. The structure-activity relationships of each compound were discussed in relation to minimum inhibitory concentrations, penicillin-binding protein (PBP) affinity and outer membrane permeability coefficient in E. coli. In this microorganism, PBP 2 was the target for all compounds. Changes in stereoisomerism influenced the affinity for PBPs 1A/B and 2. All antibiotics easily permeated the outer membrane of E. coli and, within each group of compounds, the penetration rate correlated with the antibacterial activity.     

Hybrid Photonic Nanostructures by In Vivo Incorporation of an Organic Fluorophore into Diatom Algae

Biotechnological processes harnessing living organisms' metabolism are low‐cost routes to nanostructured materials for applications in photonics, electronics, and nanomedicine. In the pursuit of photonic biohybrids, diatoms microalgae are attractive given the properties of the porous micro‐to‐nanoscale structures of the biosilica shells (frustules) they produce. The investigations have focused on in vivo incorporation of tailored molecular fluorophores into the frustules of Thalassiosira weissflogii diatoms, using a procedure that paves the way for easy biotechnological production of photonic nanostructures. The procedure ensures uniform staining of shells in the treated culture and permits the resulting biohybrid photonic nanostructures to be isolated with no damage to the dye and periodic biosilica network. Significantly, this approach ensures that light emission from the dye embedded in the isolated biohybrid silica is modulated by the silica's nanostructure, whereas no modulation of photoluminescence is observed upon grafting the fluorophore onto frustules by an in vitro approach based on surface chemistry. These results pave the way to the possibility of easy production of photonic nanostructures with tunable properties by simple feeding the diatoms algae with tailored photoactive molecules.