110 research outputs found
Palermo, metropolitan mainstreams with a twist
Palermo, administrative capital of Sicily, with its metropolitan region, hosts around one million people. A city with long history which
has been, for long periods, one of the richest cities in Europe. At
the end of the first millennium, during the Arab domination, Palermo was described as the most beautiful and happy city in the
world. An history of multifaceted dominations the one following the
other.
In XXth century, the worst days had come. After the the world wars,
Palermo was one of the cities in Italy which couldnât - or wouldnât
- step out of post-war era. The city grew, but who decided how
wasnât the public interest: from the country the Mafiosi had come,
willing to take their place in the city. And it was them, with the complicity of the leading political class, to draw the city to come.
Remember Vito Ciancimino, member of Democrazia Cristiana,
major in the seventies, the one who signed - in just one night - for
the demolition of numbers of liberty villas, to be substituted by condominiums. Another paradigmatic story regards the airport, built
during the 50s. The technicians had suggested to build it on the
east of the metropolitan area, but mysterious powers moved it to
the other side, shifting the growth of the city to lands bought at low
prices by the Mafia. Who paid the bill? In 1972, when technological aids for flight were not developed, the Alitalia 112 flight collided
with Montagna Longa, a mountain near the airport. 115 victims of
the Mafia, not even acknowledged as that.
And the city? The historical centre, one of the biggest and richest
in Europe, remained abandoned, restructuring being less profitable than building new neighbourhoods.
In the 90s, with the first left-wing administrations of its history, the
city had its âspringâ. In consequence of 1992 Mafia slaughters, the
city reacted, a new season had begun. Buildings destroyed since
second world war started to be restructured, the focus moved to
the historical centre, a detailed plan was designed, local development was launched with partial results.
With the new millennium the spring has shifted to a new autumn. A
new administration, right-wing sided, promoted the building - more
often the design - of infrastructures and flag projects. But suddenly
something happened. A major known just for his wild nights - made
of alcohols and young ladies -, dozens of scandals - for instance
those regarding the management of waste -, fiscal crisis, a second mandate coming from debated elections - pre-empted ballotpapers were found, judicial enquiries are questioning the validity
of the process - have undermined the credibility of the administration. Thus, everything seems blocked, the city is stuck, mainstream pressures are slowed by a viscous atmosphere. What has
not stopped is private led neighbourhoods upgrading.
Palermoâs metropolitan mainstream are going on, but ancient drifts
deviate them. Everything reveals backsides, contradiction is normality. Resistance appears where you may not imagine. Weâve
tried to show it in the map, where some stories are strangely mixed,
some narratives pertaining to different categories than usual.
Palermo, Southern Europe, Metropolitan Mainstream with a twis
New organotin(IV) complexes with L-Arginine,Nα-t-Boc-L-Arginine and L-Alanyl-L-Arginine.Synthesis, structural investigations and cytotoxic activity
Novel diorganotin(IV) derivatives of L-Arginine (HArg), Nα-(tert-Butoxycarbonyl)-L-Arginine (Boc-Arg-OH) and L-Ala-L-Arg (H2Ala-Arg), H2NC(=NH)NH(CH2)3CH(NHR)CO2H, where R = H in HArg, R = C(O)OC(CH3)3 in Boc-Arg-OH, R = H2NCH(CH3)CO in H2Ala-Arg and triorganotin(IV) derivatives of Boc-Arg-OH have been synthesized and structurally characterized. The complexes were investigated by FT-IR and 119Sn Mössbauer in the solid state and by 1H, 13C, 119Sn and 1H-1H COSY NMR spectroscopy, in solution. The spectroscopic characterization leading to the proposed molecular structures was accomplished on the basis of these experiments. L-Arginine appears to behave as a chelating ligand through carboxylate and -NH2 groups in Me2Sn(Arg)2, while in N-t-Boc-L-Arginine complex, the N-protected amino group being exempted from coordination, only the carboxylate groups are effectors of bonding to the organometallic moieties. FT-IR spectra give a clear indication that guanidino groups in all the complexes are not involved in coordination, since (C=N-H) frequency of the terminal guanidino group is fairly constant and unshifted relative to the free ligand. The biological activity of organotin(IV)-complexes was also investigated by use of human HT29 colorectal carcinoma cells. The cytotoxic activity of the compounds was determined by the MTT quantitative colorimetric assay, capable of detecting viable cells in comparison with that exerted by cisplatin. A marked cytotoxic activity for nearly all complexes, is evident being higher than that exerted by cisplatin, while no significant improvement of activity was observed for Me2Sn(Arg)2 and Me2Sn(Ala-Arg), which was confirmed by IC50 values. Then, we assessed whether the cytotoxicity induced by organotin(IV) complexes was associated with the induction of apoptosis. Light microscopy analysis, performed to study the morphological changes induced in HT29 cells, confirmed the results obtained with MTT test. No significant morphological alterations were observed in HT29 cells after treatment with Me2Sn(Ala-Arg) and Me2Sn(L-Arg)2. Cells treated with nBu2Sn(Boc-Arg)2, nBu2Sn(Ala-Arg), nBu3Sn(Boc-Arg) and Me3Sn(Boc-Arg), appeared rounded, isolated and detached from culture substrate, indicating the commitment to apoptotic cell death
Synthesis, structural characterisation and biological studies of new mononuclear platinum(II) complexes with sterically hindered heterocyclic ligands
Three novel cisplatin analogues were synthesized, designed according to an approach which violates
the ââclassicalââ structureâactivity relationship, by replacing the diamine ligands with a planar N donor
heterocycle giving a sterically hindered complex. Moreover, the sterical hindrance of antitumor drug
candidates potentially makes them less susceptible to deactivation by sulphur-containing proteins
and helping to overcome resistance mechanisms. The resulting mononuclear complexes of sterically
hindered polidentate heterocyclic N ligands [PtCl(bbp)]Cl (1) [bbp = 2,6-bis(2-benzimidazolyl)pyridine],
[PtCl2(dptdn)](H2O) (2) [dptdn = sodium 5,6-diphenyl-3-(20-pyridyl)-1,2,4-triazine-400,400 0-disulfonate]
and [(dptdn)(dpt)Pt]Cl2(H2O) (3) [dpt = 5,6-diphenyl-3-(20-pyridyl)-1,2,4-triazine] have been prepared
and structurally characterised. Both neutral and ionic complexes are present, with monofunctional
(1) and bifunctional Pt(II) moieties (2) and coordinatively saturated Pt(II) ions in the mixed ligand complex
(3), whose size and shape enable them to behave as novel scaffolds for DNA binding. All complexes
were tested ââin vitroââ for their biological activity on human HT29 colorectal carcinoma and HepG2 hepatoma
cells. The complexes (1) and (3), endowed with a positive charge, showed a potent cytotoxic
activity and reduced cell viability with an efficacy higher than that of cisplatin; whilst the neutral
bifunctional compound (2) was inactive. IC50 values have been calculated for the active compounds.
The cytotoxic effects were confirmed by the accumulation of treated cells in subG0/G1 phase of cell
cycle, by the loss of mitochondrial potential (Dwm) and by the chromatin condensation or fragmentation
observed by means of fluorescence microscopy after Hoechst 33258 nuclear staining. A study on
intracellular platinum uptake in HT29 cell line has been also performed and data obtained strongly
suggest that the cytotoxicity of new tested complexes reported in this work is based on a different
pharmacodynamic pattern with respect to cisplatin
Synthesis of platinum complexes with 2-(5-perfluoroalkyl-1,2,4-oxadiazol-3yl)-pyridine and 2-(3-perfluoroalkyl-1-methyl-1,2,4-triazole-5yl)-pyridine ligands and their in vitro antitumor activity
Five new mononuclear Pt(II) complexes with 5-perfluoroalkyl-1,2,4-oxadiazolyl-pyridine and 3-perfluoroalkyl-1,2,4-triazolyl-pyridine ligands are reported. The ligands 2-(5-perfluoroheptyl-1,2,4-oxadiazole-3yl)-pyridine (pfhop), 2-(5-perfluoropropyl)-1,2,4-oxadiazole-3yl)-pyridine (pfpop), 2-(3-perfluoroheptyl-1-methyl-1,2,4-triazole-5yl)-pyridine (pfhtp), 2-(3-perfluoropropyl-1-methyl-1,2,4-triazole-5yl)-pyridine (pfptp) and their complexes [PtCl2(pfhop)(2)]center dot 1.5 DMSO (2a), [PtCl2(pfpop)(2)]center dot 1.5 DMSO (3a), [PtCl2(pfhtp)(2)]center dot 1.5 DMSO (4a), PtCl2(pfhtp) (4b), [PtCl2(PfPtP)(2)]center dot 1.5 DMSO (5a) have been synthesized and structurally characterized. The complexes 2a, 3a, 4a and 5a have the same chemical environment of Pt(II) where PtCl2 moieties coordinate two molecules of ligand via N1 atom of pyridine in the case of pfhop and pfpop, and N2 atom of 1,2,4-triazole in the case of pfhtp and pfptp. For 4b, pfhtp behaves as bidentate ligand, coordinating Pt(II) ion via N4 atom of triazole and N1 atom of pyridine. All complexes have been tested in vitro by 3-(4,5-dimethyl-2-thiazolyl)bromide-2,5-diphenyl-2 H-tetrazolium (MTT) test on four tumor cell lines MCF-7 (human breast cancer), HepG2 (human hepatocellular carcinoma), HCT116 (human colorectal carcinoma). Compounds 2a and 4b showed a dose-dependent anti-proliferative effect against the three tumor cell lines whereas did not affect viability of intestinal normal-like differentiated Caco-2 cells. The cell death of HepG2, MCF-7 and HCT116 induced by the compounds, was considered to be apoptotic by measuring the exposure of phosphatidylserine to the outer membrane and observing the typical apoptotic morphological change by acridine orange (AO)/ethidium bromide (EB) stainin
Synthesis, characterization, crystal structures and in vitro antistaphylococcal activity of organotin(IV) derivatives with 5,7-disubstituted-1,2,4-triazolo[1,5-a]pyrimidine
New organotin(IV) complexes of 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp) and 5,7-diphenyl- 1,2,4-triazolo[1,5-a]pyrimidine (dptp) with 1:1 and/or 1:2 stoichiometry were synthesized and investigated by X-ray diffraction, FT-IR and 119Sn Mössbauer in the solid state and by 1H and 13C NMR spectroscopy, in so- lution. Moreover, the crystal and molecular structures of Et2SnCl2(dbtp)2 and Ph2SnCl2(EtOH)2(dptp)2 are reported. The complexes contain hexacoordinated tin atoms: in Et2SnCl2(dbtp)2 two 5,7-ditertbutyl-1,2,4- triazolo[1,5-a]pyrimidine molecules coordinate classically the tin atom through N(3) atom and the coordina- tion around the tin atom shows a skew trapezoidal structure with axial ethyl groups. In Ph2SnCl2(EtOH)2 (dptp)2 two ethanol molecules coordinate tin through the oxygen atom and the 5,7-diphenyl-1,2,4-triazolo [1,5-a]pyrimidine molecules are not directly bound to the metal center but strictly H-bonded, through N (3), to the \OH group of the ethanol moieties; Ph2SnCl2(EtOH)2(dptp)2 has an all-trans structure and the CâSnâC fragment is linear. On the basis of Mössbauer data, the 1:2 diorganotin(IV) complexes are advanced to have the same structure of Et2SnCl2(dbtp)2, while Me2SnCl2(dptp)2 to have a regular all-trans octahedral structure. A distorted cis-R2 trigonal bipyramidal structure is assigned to 1:1 diorganotin(IV) complexes. The in vitro antibacterial activities of the synthesized complexes have been tested against a group of reference pathogen micro-organisms and some of them resulted active with MIC values of 5 ÎŒg/mL, most of all against staphylococcal strains, which shows their inhibitory effect
Pt(II) complex @mesoporous silica: preparation, characterization and study of release
Cisplatin analogs, having cytotoxic activity higher than that exerted by cisplatin, have recently triggered considerable interest by the
community. The cis-[PtCl2(DMSO)HL]·2DMSO, where HL = 7-amino-2-(methylthio)[1,2,4]triazolo[1,5-a]pyrimidine-6-carboxylic
acid, has shown a potent cytotoxic activity on HepG2 hepatocarcinoma cells, while under identical conditions, it did not affect normal
immortalized human liver cells (Chang). In this work, the above complex has been incorporated into MCM41 mesoporous silica, pure
and functionalized with amino group, which is considered one of the best host for a drug delivery system for carrying high dosages of a
variety of drugs in their mesopores. Since the controlled release of an anticancer drug helps to maintain its therapeutic level for an
extended time period while minimizing undesirable high peaks immediately following administration, the in vitro tests have been
performed in order to obtain the corresponding drug release profile. The investigated system demonstrated to be an efficient system for
pharmaceutic controlled release. A deepened characterization of the systems has been performed in order to known their structure and
features and to speculate the mechanisms involved in the release
Superoxide Dismutase-1 intracellular content in T lymphocytes associates with increased Regulatory T Cell level in Multiple Sclerosis subjects undergoing immune-modulating treatment.
Reactive oxygen species (ROS) participate in the T-cell activation processes. ROS-dependent regulatory networks are usually mediated by peroxides, which are more stable and able to freely migrate inside cells. Superoxide dismutase (SOD)-1 represents the major physiological intracellular source of peroxides. We found that antigen-dependent activation represents a triggering element for SOD-1 production and secretion by human T lymphocytes. A deranged T-cell proinflammatory response characterizes the pathogenesis of multiple sclerosis (MS). We previously observed a decreased SOD-1 intracellular content in leukocytes of MS individuals at diagnosis, with increasing amounts of such enzyme after interferon (IFN)-b 1b treatment. Here, we analyzed in depth SOD-1 intracellular content in T cells in a cohort of MS individuals undergoing immune-modulating treatment. Higher amounts of the enzyme were associated with increased availability of regulatory T cells (Treg) preferentially expressing Foxp3-exon 2 (Foxp3-E2), as described for effective Treg. In vitro administration of recombinant human SOD-1 to activated T cells, significantly increased their IL-17 production, while SOD-1 molecules lacking dismutase activity were unable to interfere with cytokine production by activated T cells in vitro. Furthermore, hydrogen peroxide addition was observed to mimic, in vitro, the SOD-1 effect on IL-17 production. These data add SOD-1 to the molecules involved in the molecular pathways contributing to re-shaping the T-cell cytokine profile and Treg differentiation
T cell activation induces CuZn Superoxide Dismutase (SOD)-1) intracellular re-localization, production and secretion
Reactive Oxygen Species (ROS) behave as second messengers in signal transduction for a series of receptor/ligand interactions. A major regulatory role is played by hydrogen peroxide (H2O2), more stable and able to freely diffuse through cell membranes. CuZn Superoxide dismutase (SOD)-1 is a cytosolic enzyme involved in scavenging oxygen radicals to H2O2 and molecular oxygen, thus representing a major cytosolic source of peroxides. Previous studies suggested that superoxide anion and H2O2 generation are involved in T Cell Receptor (TCR)-dependent signaling.
Here, we describe that antigen-dependent activation of human T lymphocytes significantly increased extracellular SOD-1 levels in lymphocyte cultures. This effect was accompanied by the synthesis of SOD-1-specific mRNA and by the induction of microvesicle SOD-1 secretion. It is of note that SOD-1 increased its concentration specifically in T cell population, while no significant changes were observed in the ânon Tâ cell counterpart. Moreover, confocal microscopy showed that antigen-dependent activation was able to modify SOD-1 intracellular localization in T cells. Indeed, was observed a clear SOD-1 recruitment by TCR clusters. The ROS scavenger N-acetylcysteine (NAC) inhibited this phenomenon. Further studies are needed to define whether SOD-1-dependent superoxide/peroxide balance is relevant for regulation of T cell activation, as well as in the functional cross talk between immune effectors
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