Publications by authors named "Luca Conti"

35 Publications

Exploring the potential of highly charged Ru(II)- and heteronuclear Ru(II)/Cu(II)-polypyridyl complexes as antimicrobial agents.

J Inorg Biochem 2021 Jul 22;220:111467. Epub 2021 Apr 22.

Department of Chemistry "Ugo Schiff", University of Florence, via della Lastruccia 3, 50019 Sesto Fiorentino, Italy.

The antimicrobial potential of two ruthenium(II) polypyridyl complexes, [Ru(phen)L1] and [Ru(phen)L2] (phen = 1,10-phenanthroline) containing the 4,4'-(2,5,8,11,14-pentaaza[15])-2,2'-bipyridilophane (L1) and the 4,4'-bis-[methylen-(1,4,7,10-tetraazacyclododecane)]-2,2' bipyridine (L2) units, is herein investigated. These peculiar polyamine frameworks afford the formation of highly charged species in solution, influence the DNA-binding and cleavage properties of compounds, but they do not undermine their singlet oxygen sensitizing capacities, thus making these complexes attractive O generators in aqueous solution. L1 and L2 also permit to stably host Fenton -active Cu ion/s, leading to the formation of mixed Ru/Cu forms capable to further strengthen the oxidative damages to biological targets. Herein, following a characterization of the Cu binding ability by [Ru(phen)L2], the water-octanol distribution coefficients, the DNA binding, cleavage and O sensitizing properties of [Ru(phen)L2] and [CuRu(phen)L2] were analysed and compared with those of [Ru(phen)L1] and [CuRu(phen)L1]. The antimicrobial activity of all compounds was evaluated against B. subtilis, chosen as a model for gram-positive bacteria, both under dark and upon light-activation. Our results unveil a notable phototoxicity of [Ru(phen)L2] and [CuRu(phen)L2], with MIC (minimal inhibitory concentrations) values of 3.12 μM. This study highlights that the structural characteristics of polyamine ligands gathered on highly charged Ru(II)-polypyridyl complexes are versatile tools that can be exploited to achieve enhanced antibacterial strategies.
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http://dx.doi.org/10.1016/j.jinorgbio.2021.111467DOI Listing
July 2021

Necrotic papules of the elbows as a dermatologic manifestation of eosinophilic granulomatosis with polyangiitis.

Ital J Dermatol Venerol 2021 Apr 23. Epub 2021 Apr 23.

Dermatology Clinic, Medical Sciences Department, University of Turin, Turin, Italy.

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http://dx.doi.org/10.23736/S2784-8671.21.06902-9DOI Listing
April 2021

Exploring the Ability of Luminescent Metal Assemblies to Bind and Sense Anionic or Ionizable Analytes A Ru(phen)bipy-Based Dizinc Complex for Bisphenol A (BPA) Recognition.

Molecules 2021 Jan 20;26(3). Epub 2021 Jan 20.

Department of Chemistry "Ugo Schiff", Università degli Studi di Firenze, via della Lastruccia 3, 50019 Sesto Fiorentino, Italy.

The synthesis of a new Ru complex, in which the metal is coordinated by two 1,10-phenanthroline ligands and a 2,2'-bipyridyl unit linked, via methylene bridges in its 4 and 4' positions, to two 1,4,7,10-tetraazacyclododecane (cyclen) macrocycles ([Ru(phen)]) is reported. Protonation and Zn binding by [Ru(phen)] have been analyzed by potentiometric titration, evidencing the formation of mixed hetero-binuclear and hetero-trinuclear Zn/Ru complexes. These complexes were tested as bis-phenol A (BPA) binders. Only the dizinc complex with [Ru(phen)] is able to bind BPA in aqueous solution, affording a remarkably stable {Zn[Ru(phen)]BPA(H)} adduct at neutral pH, in which BPA is bound in its doubly deprotonated form to the two Zn ions. BPA binding was found to quench the luminescence emission of the Ru(phen)bipy core. Although the quenching effect is modest, this study demonstrates that appropriately designed dizinc complexes can be used for binding and optical sensing of BPA in water.
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http://dx.doi.org/10.3390/molecules26030527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864177PMC
January 2021

A brown tumor secondary to hyperparathyroidism in the maxilla, skull, scapula, and femora.

Proc (Bayl Univ Med Cent) 2020 Oct 15;34(1):163-165. Epub 2020 Oct 15.

Department of Endocrinology, Diabetes, and General Medicine, Mater Dei Hospital, Msida, Malta.

Primary hyperparathyroidism presenting with diffuse skeletal involvement, such as discrete osteoclastic bone lesions, is rare. We describe a 35-year-old woman who presented with a left mandibular mass that rapidly enlarged over 3 weeks. Radiological, histological, and biochemical investigations led to the diagnosis of brown tumor secondary to primary hyperparathyroidism. A neck ultrasound revealed a 1.5 × 2.3 × 4.6 cm mass at the lower pole of the left thyroid lobe, suggestive of a parathyroid adenoma. Bone scan showed additional abnormal foci of increased uptake in the maxilla, both femora, skull, and scapula. Brown tumors are treated primarily by correcting the underlying endocrine disorder, and a parathyroidectomy was performed.
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http://dx.doi.org/10.1080/08998280.2020.1826260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785168PMC
October 2020

A Case of a Pigmented Epithelioid Melanocytoma on a Mucosal Site.

Dermatol Pract Concept 2020 Oct 26;10(4):e2020070. Epub 2020 Oct 26.

Dermatology Clinic and Surgical Pathology Section, Department of Medical Sciences, University of Turin, Italy.

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http://dx.doi.org/10.5826/dpc.1004a70DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7588147PMC
October 2020

Switching on the Fluorescence Emission of Polypyridine Ligands by Simultaneous Zinc(II) Binding and Protonation.

Chempluschem 2020 04;85(4):659-671

Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino, Italy.

The synthesis and characterization of the two new open-chain ligands 1,15-bis-[6-(2,2'-bipyridyl)]-2,5,8,11,14-pentaaza-octadecane (L1) and 1,15-bis-[2-(1,10-phenanthroline)-9-methyl]-2,5,8,11,14-pentaazaoctadecane (L2), both featuring a tetraethylenpentaamine chain linking via methylene bridges the 6 and 2 positions of two identical 2,2'-bipyridyl (bpy) and 9-methyl-1,10-phenanthroline (9-methyl-phen) moieties respectively, are reported. Their protonation and binding ability for Cu , Zn , Cd and Pb have been studied by coupling potentiometric titrations with UV-vis absorption and fluorescence emission measurements in water. L1 and L2 afford stable mono- and dinuclear complexes, in which the metal ion is bound by a single bpy or 9-methyl-phen unit and the amine groups on the aliphatic chain. However, L1 displays a greater binding ability for Cu and Zn with respect to L2, the stability constants of the [ML1] complexes being 21.8 (Cu ) and 19.4 (Zn ) log units vs 20.34 and 16.8 log. units for the corresponding L2 species. Among all the metal ions tested, only the Zn complex with L2 features an enhanced fluorescence emission at neutral pH, thanks to the simultaneous binding of one Zn ion and H ion(s), that inhibits any possible photoinduced electron transfer (PET) process from the amine donors to the excited phen moiety. Binding of a second metal switches off the emission again.
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http://dx.doi.org/10.1002/cplu.201900752DOI Listing
April 2020

Playing with Structural Parameters: Synthesis and Characterization of Two New Maltol-Based Ligands with Binding and Antineoplastic Properties.

Molecules 2020 Feb 20;25(4). Epub 2020 Feb 20.

Department of Pure and Applied Sciences, University of Urbino "Carlo Bo", via della Stazione 4, 61029 Urbino, Italy.

Two maltol-based ligands, ,'-bis((3-hydroxy-4-pyron-2-yl)methyl)-1,4-piperazine () and ,','-tris((3-hydroxy-4-pyron-2-yl)methyl)--methylethylendiamine (), were synthesized and characterized. and , containing, respectively, two and three maltol units spaced by a diamine fragment, were designed to evaluate how biological and binding features are affected by structural modifications of the parent compound malten. The acid-base behavior and the binding properties towards transition, alkaline-earth (AE) and rare-earth (RE) cations in aqueous solution, studied by potentiometric, UV-Vis and NMR analysis, are reported along with biological studies on DNA and leukemia cells. Both ligands form stable complexes with Cu(II), Zn(II) and Co(II) that were studied as metallo-receptors for AE and RE at neutral pH. complexes are more affected than ones by hard cations, the -Cu(II) system being deeply affected by RE. The structural modifications altered the mechanism of action: partially maintains the ability to induce structural alterations of DNA, while provokes single strand (nicks) and to a lesser extent double strand breaks of DNA.
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http://dx.doi.org/10.3390/molecules25040943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070877PMC
February 2020

Kounis syndrome uncovers severe coronary disease: an unusual case of acute coronary syndrome secondary to allergic coronary vasospasm.

BMJ Case Rep 2019 Dec 23;12(12). Epub 2019 Dec 23.

Department of Medicine, Mater Dei Hospital, Msida, Malta.

Acute coronary syndrome occurring during the course of a type I hypersensitivity reaction constitutes Kounis syndrome. We report a case of a 64-year-old man who presented with a non-ST elevation myocardial infarction and peripheral blood eosinophilia. He had rhinitis and constitutional symptoms for several days prior to presentation. Blood investigations revealed moderate eosinophilia and elevated IgE levels. A cardiac MRI showed generalised oedema with a subtle wall motion abnormality in basal inferior/inferolateral wall, and subendocardial high signal on late gadolinium enhancement suggesting a localised myocardial infarction. A coronary angiogram then revealed triple vessel disease. A diagnosis of Kounis syndrome was made. Within days of starting appropriate treatment, the patient's eosinophil count returned to normal with improvement of clinical picture.
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http://dx.doi.org/10.1136/bcr-2019-232472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936473PMC
December 2019

Superimposed esophageal pemphigus vulgaris and herpes simplex infection.

Ann Gastroenterol 2019 Nov-Dec;32(6):654. Epub 2019 Jul 25.

Department of Gastroenterology (Kelly Gatt, Luca Conti, Pierre Ellul).

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http://dx.doi.org/10.20524/aog.2019.0408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826074PMC
July 2019

Clinical and Pathological Relevance of Drug-induced Vitiligo in Patients Treated for Metastatic Melanoma with Anti-PD1 or BRAF/MEK Inhibitors.

Acta Derm Venereol 2020 01 7;100(1):adv00001. Epub 2020 Jan 7.

Department of Medical Sciences, Dermatologic Clinic, Turin, Italy.

Current therapies for metastatic melanoma (anti-PD1 and BRAF/MEK inhibitors) can cause drug-induced vitiligo. The aim of this study is to dermatologically define and histologically characterize this new type of vitiligo, and assess the clinical course of the disease. Fourteen patients with metastatic melanoma treated with immune or targeted therapy were included in a dataset evaluating clinical data, vitiligo description and histopathological features. Vitiligo-like lesions occurred after a mean of 7.5 months from the start of the therapies (range 1-42 months), with a prevalence of the non-segmental variant (71.4%). Fifty percent of patients showed a clinical response (4 complete response and 3 partial response), 35.7% had stable disease, and one patient died after disease progression. Median survival from the start of the therapies was 32.5 months. Drug-induced vitiligo can be related to both immune and targeted therapies, is associated with a favourable prognosis, and has clinical characteristics different from the classical form.
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http://dx.doi.org/10.2340/00015555-3319DOI Listing
January 2020

Different Antioxidant Efficacy of Two Mn-Containing Superoxide Anion Scavengers on Hypoxia/Reoxygenation-Exposed Cardiac Muscle Cells.

Sci Rep 2019 07 16;9(1):10320. Epub 2019 Jul 16.

Department of Experimental & Clinical Medicine, Research Unit of Histology & Embryology, University of Florence, viale G. Pieraccini 6, 50139, Florence, Italy.

Oxidative stress due to excess superoxide anion ([Formula: see text]) produced by dysfunctional mitochondria is a key pathogenic event of aging and ischemia-reperfusion diseases. Here, a new [Formula: see text]-scavenging Mn complex with a new polyamino-polycarboxylate macrocycle (4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diacetate) containing 2 quinoline units (MnQ2), designed to improve complex stability and cell permeability, was compared to parental Mn complex with methyls replacing quinolines (MnM2). MnQ2 was more stable than MnM2 (log K = 19.56(8) vs. 14.73(2) for the equilibrium Mn + L, where L = Q2 and M2) due to the involvement of quinoline in metal binding and to the hydrophobic features of the ligand which improve metal desolvation upon complexation. As oxidative stress model, H9c2 rat cardiomyoblasts were subjected to hypoxia-reoxygenation. MnQ2 and MnM2 (10 μmol L) were added at reoxygenation for 1 or 2 h. The more lipophilic MnQ2 showed more rapid cell and mitochondrial penetration than MnM2. Both MnQ2 and MnM2 abated endogenous ROS and mitochondrial [Formula: see text], decreased cell lipid peroxidation, reduced mitochondrial dysfunction, in terms of efficiency of the respiratory chain and preservation of membrane potential (Δψ) and permeability, decreased the activation of pro-apoptotic caspases 9 and 3, and increased cell viability. Of note, MnQ2 was more effective than MnM2 to exert cytoprotective anti-oxidant effects in the short term. Compounds with redox-inert Zn replacing the functional Mn were ineffective. This study provides clues which further our understanding of the structure-activity relationships of Mn-chelates and suggests that Mn-polyamino-polycarboxylate macrocycles could be developed as new anti-oxidant drugs.
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http://dx.doi.org/10.1038/s41598-019-46476-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635543PMC
July 2019

Phenotypic characterisation of immune cells associated with histological regression in cutaneous melanoma.

Pathology 2019 Aug 29;51(5):487-493. Epub 2019 Jun 29.

Department of Medical Sciences, Section of Dermatology, University of Turin, Torino, Italy; Dermatologic Surgery Section, Department of Oncology, AOU Città della Salute e della Scienza di Torino, Torino, Italy.

Histological regression and tumour infiltrating lymphocytes represent an early sign of activation of the immune system against primary melanoma. The first phenomenon has been especially discussed in the literature because of its prognostic role, but no clear agreement on its evaluation has been reached. Immunotherapy of advanced stage melanoma has recently shown promising results; an improved understanding of the initial interplay between melanoma cells and the immune system would potentially help tailor treatment for patients. Seventy consecutive melanomas with regression were analysed to identify a prognostic cut-off value of regression extension. Then, we compared the immune infiltrate between regressed and not regressed areas of these regressed melanomas, assessing CD3, CD4, CD8, CD20, CD123, PD1 and FOXP3/CD25 expression. The immune infiltrate of these cases was further compared with 28 control melanomas without regression. A regression extension of 10% represented a reliable cut-off to distinguish two different risk categories in regressed melanomas. Regressed areas were less infiltrated by CD4/CD25, FOXP3/CD4 or PD1/CD4 compared to not regressed areas of each sample. These lymphocyte subsets are associated with anergy and hamper the immune CD8+ response towards the cancer cells. Moreover, the relevance of these findings was further supported by the observation that not regressed controls were significantly more infiltrated by these anergic immune cell subsets compared to the regressed cases. These results help understand the real meaning of regression in melanoma. Moreover, the association here identified between specific immunomodulatory immune cell subsets and regression could help in developing new therapeutic strategies.
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http://dx.doi.org/10.1016/j.pathol.2019.04.001DOI Listing
August 2019

A new crystal form of the NSAID dexketoprofen.

Acta Crystallogr C Struct Chem 2019 Jun 28;75(Pt 6):783-792. Epub 2019 May 28.

Department of Chemistry `Ugo Schiff', University of Florence, Via della Lastruccia 3, Sesto Fiorentino-FI, I-50019, Italy.

Dexketoprofen [(2S)-2-(3-benzoylphenyl)propanoic acid], CHO, is the S-enantiomer of ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID) that has analgesic, antipyretic and anti-inflammatory properties, and finds applications for the short-term treatment of mild to moderate pain. A new crystalline phase of dexketoprofen is reported. Its solid-state structure was determined by single-crystal X-ray diffraction (SCXRD). The molecular structure of the two independent molecules found in the asymmetric unit of this new phase (DXKP-β) were compared to those of the already known crystal form of dexketoprofen (DXKP-α) and with the S-enantiomer of the racemic compound. The three different conformers of dexketoprofen found in DXKP-α and DXKP-β were then investigated by computational methods. The optimized structures are very close to the corresponding starting geometries and do not differ significantly in energy. The crystal packing of DXKP-β was studied by means of Hirshfeld surface (HS) analysis; interaction energies were also calculated. A comparison with DXKP-α shows close similarities between the two crystal forms, i.e. in both cases, molecules assemble through the catemer O-H...O synthon of the carboxylic acid stabilized by additional C-H...O contacts and, accordingly, the interaction energies, as well as the contributions to the HS area, are very similar. Finally, the thermal behaviour of the two polymorphs of dexketoprofen was assessed by means of XRD (both from single crystal and microcrystalline powder) and differential scanning calorimetry (DSC); both crystal forms are stable under the experimental conditions adopted (air, 300-350 K for DXKP-α and 300-340 K DXKP-β) and no solid-solid phase transition occurs between the two crystal forms in the investigated temperature range (from 100 K up to ca 350 K).
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http://dx.doi.org/10.1107/S2053229619006533DOI Listing
June 2019

Highly Charged Ruthenium(II) Polypyridyl Complexes as Effective Photosensitizer in Photodynamic Therapy.

Chemistry 2019 Aug 2;25(45):10606-10615. Epub 2019 Jul 2.

Department of Chemistry 'Ugo Schiff', University of Florence, Via della Lastruccia 3, 50019, Sesto Fiorentino (FI), Italy.

A comparative study between two novel, highly water soluble, ruthenium(II) polypyridyl complexes, [Ru(phen) L'] and [Ru(phen) Cu(II)L'] (L and L-Cu ), containing the polyaazamacrocyclic unit 4,4'-(2,5,8,11,14-pentaaza[15])-2,2'-bipyridilophane (L'), is herein reported. L and L-Cu interact with calf-thymus DNA and efficiently cleave DNA plasmid when light-activated. They also possess great penetration abilities and photo-induced biological activities, evaluated on an A375 human melanoma cell line, with L-Cu being the most effective. Our study highlights the key role of the Fenton active Cu center within the macrocycle framework, that would play a synergistic role with light activation in the formation of cytotoxic ROS species. Based on these results, an optimal design of Ru polypyridyl systems featuring specific Cu -chelating polyamine units could represent a suitable strategy for the development of novel and effective photosensitizers in photodynamic therapy.
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http://dx.doi.org/10.1002/chem.201901570DOI Listing
August 2019

Incidental tracheal bronchus in a case of Hamman-Rich syndrome.

BMJ Case Rep 2019 May 14;12(5). Epub 2019 May 14.

Respiratory Department, Mater Dei Hospital, Msida, Malta.

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http://dx.doi.org/10.1136/bcr-2019-229579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536212PMC
May 2019

[9]aneN-based fluorescent receptors for metal ion sensing, featuring urea and amide functional groups.

Dalton Trans 2019 Apr;48(15):4949-4960

Dipartimento di Scienze Chimiche e Geologiche, Università degli Studi di Cagliari, S.S. 554 Bivio per Sestu, 09042, Monserrato, Italy.

We describe here the synthesis and coordination properties of three new derivatives of [9]aneN3 containing phenyl/quinoline pendant arm derivatives (L1, L2 and L3, respectively) also featuring urea (L1-L2) or amide (L3) functions as "non-innocent" spacers. At first, L1, L2 and L3 were studied considering the interaction with a series of anions (AcO-, BzO-, H2PO4-, F-, and Cl-) by means of 1H NMR measurements. Subsequently, the optical responses of L2 and L3 in the presence of several metal ions Cd2+, Co2+, Cu2+, Fe3+, Hg2+, K+, Mg2+, Mn2+, Ni2+, Zn2+ and Pb2 were analysed in MeCN/H2O (4 : 1 v/v). As observed by spectrophotometric and spectrofluorimetric titrations, there were significant changes in the absorbance and fluorescent emission of L2 upon addition of increasing amounts of Cd2+, Zn2+, Pb2+ and Cu2+ in MeCN/H2O (4 : 1 v/v). In particular, titrations of L2 with Cd2+, Zn2+ or Pb2+ showed an almost comparable CHEF effect up to an M2+/L2 molar ratio of 1. Overall, no significant optical selectivity was observed in the case of L2. Conversely, L3 revealed an OFF-ON selective response only in the presence of the Zn2+ ion in MeCN/H2O (4 : 1 v/v), which can be attributed to the formation of both 1 : 1 and 1 : 2 metal-to-ligand complexes, as also confirmed by potentiometric measurements. Finally, crystals of [ZnL1(Ac)](Ac) (1), [CuL1(Cl)](Cl)·H2O (2) and [CuL3](NO3) (3) were grown and analysed by X-ray diffraction. 1 and 3 feature the metal center in a pseudo-octahedral coordination geometry coordinated also by the carbonyl group from one pendant arm, while in the case of 2, one of the six coordination sites in the final distorted octahedral geometry is occupied by the nitrogen donor from the urea group of one pendant arm.
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http://dx.doi.org/10.1039/c9dt00288jDOI Listing
April 2019

Eccrine spiradenoma of the nipple: Case report, differential diagnosis and literature review.

Histol Histopathol 2019 Aug 26;34(8):909-915. Epub 2019 Feb 26.

Department of Medical Sciences, University of Turin, Turin, Italy.

Eccrine spiradenoma is a rare lesion originating from eccrine sweat glands, with only few cases reported in breast tissue: we here describe for the first time, an eccrine spiradenoma arising in the nipple. An 84 year-old woman with a lesion enlarging her right nipple, showing ulcerations and eczema-like changes of the covering skin, was admitted to our hospital. Surgical excision of the central quadrant with nipple-areola complex was performed, followed by histopathological evaluation which revealed an adenoma with predominantly basaloid epithelial cells. The lesion was composed of tightly packed small and large groups of cells, arranged in diffuse alveolar/pseudorosette formations. The small cells expressed p63 and calponin, while a positive expression of CK7 and CD117 was detected in large cells. After careful and detailed examination, excluding various similar entities, a diagnosis of eccrine spiradenoma has been rendered. Although extremely rare, eccrine spiradenoma should be taken into account in the differential diagnosis of subcutaneous primary breast tumors.
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http://dx.doi.org/10.14670/HH-18-094DOI Listing
August 2019

The solid-state structure of the β-blocker metoprolol: a combined experimental and in silico investigation.

Acta Crystallogr C Struct Chem 2019 Feb 15;75(Pt 2):87-96. Epub 2019 Jan 15.

Department of Chemistry `Ugo Schiff', University of Florence, Via della Lastruccia 3, Sesto Fiorentino-FI, I-50019, Italy.

Metoprolol {systematic name: (RS)-1-isopropylamino-3-[4-(2-methoxyethyl)phenoxy]propan-2-ol}, CHNO, is a cardioselective β-adrenergic blocking agent that shares part of its molecular skeleton with a large number of other β-blockers. Results from its solid-state characterization by single-crystal and variable-temperature powder X-ray diffraction and differential scanning calorimetry are presented. Its molecular and crystal arrangements have been further investigated by molecular modelling, by a Cambridge Structural Database (CSD) survey and by Hirshfeld surface analysis. In the crystal, the side arm bearing the isopropyl group, which is common to other β-blockers, adopts an all-trans conformation, which is the most stable arrangement from modelling data. The crystal packing of metoprolol is dominated by an O-H...N/N...H-O pair of hydrogen bonds (as also confirmed by a Hirshfeld surface analysis), which gives rise to chains containing alternating R and S metoprolol molecules extending along the b axis, supplemented by a weaker O...H-N/N-H...O pair of interactions. In addition, within the same stack of molecules, a C-H...O contact, partially oriented along the b and c axes, links homochiral molecules. Amongst the solid-state structures of molecules structurally related to metoprolol deposited in the CSD, the β-blocker drug betaxolol shows the closest analogy in terms of three-dimensional arrangement and interactions. Notwithstanding their close similarity, the crystal lattices of the two drugs respond differently on increasing temperature: metoprolol expands anisotropically, while for betaxolol, an isotropic thermal expansion is observed.
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http://dx.doi.org/10.1107/S2053229618017084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363042PMC
February 2019

Fluoride binding by an anionic receptor: tuning the acidity of amide NH groups for basic anion hydrogen bonding and recognition.

Chem Commun (Camb) 2019 Feb;55(19):2745-2748

Dipartimento di Scienze Chimiche e Geologiche, Università degli Studi di Cagliari, S.S. 554 Bivio per Sestu, 09042 Monserrato (CA), Italy.

Here we report a family of bis-amide receptors for anion binding that contain carboxylic acid groups vicinal to the amide function. Deprotonation of the carboxylic acids decreases the acidity of amide NHs, switching on the anion binding ability of the deprotonated receptors with selectivity for fluoride complexation. The proposed systems represent a unique example of anionic receptors able to bind anions via H-bonding.
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http://dx.doi.org/10.1039/c8cc09962fDOI Listing
February 2019

Unusual case of primary pulmonary Hodgkin's lymphoma presenting with a continuous murmur.

BMJ Case Rep 2018 Sep 28;2018. Epub 2018 Sep 28.

Respiratory Department, Mater Dei Hospital, Msida, Malta.

Systemic to pulmonary fistulas are an unusual entity, even more so in association with Hodgkin's lymphoma. We herein report a case of a 33-year-old woman that presented with an incidental lung lesion on a chest radiograph with an associated high-frequency continuous murmur over the lesion. The diagnosis of primary pulmonary Hodgkin's lymphoma, nodular sclerosis type, was obtained by a CT transthoracic biopsy. We achieved an excellent response after polychemotherapy with near-complete disappearance of the mass and a residual faint systolic murmur over the lesion.
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http://dx.doi.org/10.1136/bcr-2018-225674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6169648PMC
September 2018

Squamous-Cell Carcinoma of the Lung.

N Engl J Med 2018 Sep;379(11):e17

Mater Dei Hospital, Msida, Malta

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http://dx.doi.org/10.1056/NEJMicm1802514DOI Listing
September 2018

Treatment of Nonhealing Ulcers with an Allograft/Xenograft Substitute: A Case Series.

Adv Skin Wound Care 2018 Jul;31(7):306-309

In Linköping, Sweden, Tobias Sivlér, MD, is medical advisor and physician, S2Medical AB, Sunnorpsgatan; Petter Sivlér, MSc, is a PhD Student, Division of Molecular Physics, Department of Physics, Chemistry and Biology, Linköping University, and Chief Executive Officer, S2Medical AB, Sunnorpsgatan; Mårten Skog, MSc, is a PhD Student, Division of Molecular Physics, Department of Physics, Chemistry and Biology, Linköping University, and Chief Operational Officer, S2Medical AB, Sunnorpsgatan; Luca Conti, PhD, is Research and Development Engineer, S2Medical AB, Sunnorpsgatan; and Daniel Aili, PhD, is Assistant Professor, Division of Molecular Physics, Department of Physics, Chemistry and Biology, Linköping University.

Objective: Wound dressings that use biosynthetic cellulose may be a good alternative to dressings currently used to treat chronic and acute ulcers because their nanostructure is similar to collagen. The objective of this study was to evaluate a wound dressing created with a new material that is composed of a fibrillary network of biosynthetic cellulose.

Methods: A case series of 8 patients in primary healthcare centers in Östergötland county council, Sweden, with chronic and acute lower limb wounds were treated with a wound dressing based on eiratex (S2Medical AB, Linköping, Sweden). The dressing was applied to traumatic (n = 5) and venous ulcers (n = 3). All ulcers were considered healed at the end of the treatment.

Main Outcome Measure: The wounds were examined at regular intervals by a physician to determine healing time, number of dressing changes, and number of visits.

Main Results: Mean healing time was 43 ± 6 days after the first application of the dressing. The mean number of visits was 5.7 ± 0.6, and the mean number of dressings used per patient was 1.7 ± 0.2.

Conclusions: These results demonstrate the efficacy of a wound dressing made of eiratex to heal chronic and acute ulcers. The data show that the number of dressings used and dressing changes needed to heal the ulcers are lower than what have been reported in the literature for other dressing materials.
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http://dx.doi.org/10.1097/01.ASW.0000534701.57785.cdDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6039395PMC
July 2018

Spectroscopic and photoacoustic characterization of encapsulated iron oxide super-paramagnetic nanoparticles as a new multiplatform contrast agent.

Spectrochim Acta A Mol Biomol Spectrosc 2018 Jun 15;199:248-253. Epub 2018 Mar 15.

Istituto di Fisiologia Clinica, CNR, Via Giuseppe Moruzzi 1, Pisa 56124, Italy. Electronic address:

Recently, a number of photoacoustic (PA) agents with increased tissue penetration and fine spatial resolution have been developed for molecular imaging and mapping of pathophysiological features at the molecular level. Here, we present bio-conjugated near-infrared light-absorbing magnetic nanoparticles as a new agent for PA imaging. These nanoparticles exhibit suitable absorption in the near-infrared region, with good photoacoustic signal generation efficiency and high photo-stability. Furthermore, these encapsulated iron oxide nanoparticles exhibit strong super-paramagnetic behavior and nuclear relaxivities that make them useful as magnetic resonance imaging (MRI) contrast media as well. Their simple bio-conjugation strategy, optical and chemical stability, and straightforward manipulation could enable the development of a PA probe with magnetic and spectroscopic properties suitable for in vitro and in vivo real-time imaging of relevant biological targets.
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http://dx.doi.org/10.1016/j.saa.2018.03.025DOI Listing
June 2018

Mitochondrial DNA "common deletion" in post-fine needle aspiration infarcted oncocytic thyroid tumors.

Hum Pathol 2017 11 27;69:23-30. Epub 2017 Sep 27.

Department of Oncology, University of Torino, Città della Salute e della Scienza Hospital, 10126 Torino, Italy.

Thyroid fine needle aspiration (FNA) can rarely induce morphological changes potentially hindering the histopathological diagnosis, especially in Hurthle cell tumors (HCTs), which may easily undergo post-FNA infarction or necrosis. HCTs contain mitochondrion (mt)-rich cells that may bear mtDNA mutations, the most frequent being the so-called common deletion (CD). The aim of this study was to determine the presence and extent of the mtDNA CD in a series of thyroid HCTs that underwent extensive infarction following FNA procedure in comparison with a control series of HCTs lacking post-FNA ischemic/hemorrhagic alterations. Of 257 HCTs with available matched FNA and surgical specimens, 8 cases showed extensive (≥80%) infarction or necrosis in the resected nodule (4 adenomas, 1 carcinoma, 3 HCTs undefined for malignancy). Noninfarcted tumors in the control series included 9 adenomas, 1 carcinoma, and 1 follicular tumor of uncertain malignant potential. These lesions were significantly (P = .03) larger than infarcted nodules. The mtDNA CD was identified using semiquantitative real-time polymerase chain reaction in 2 of 8 (25%) infarcted tumors. In HCTs lacking infarction/necrosis of the control series, the CD was significantly (P = .05) more common (8/11 cases, 72.7%). In 7 of the 10 deleted cases, the CD was present also in the adjacent nonneoplastic parenchyma. In conclusion, the rare oncocytic tumors undergoing extensive infarction are smaller than those lacking ischemic changes and bear the mtDNA CD in a significantly lower proportion compared with control noninfarcted HCTs. This may suggest that mtDNA deletion confers a survival advantage to oncocytic cells in stress conditions, including FNA procedures.
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http://dx.doi.org/10.1016/j.humpath.2017.09.004DOI Listing
November 2017

Methylene blue-containing liposomes as new photodynamic anti-bacterial agents.

J Mater Chem B 2017 Apr 29;5(15):2788-2797. Epub 2017 Mar 29.

Department of Experimental & Clinical Medicine, Research Unit of Histology & Embryology, University of Florence, Italy.

Methylene blue (MB) can be employed as a photo-activatable antimicrobial drug in photodynamic therapy (PDT) due to its ability to release oxygen free radicals upon photo-activation. However, its poor ability to penetrate bacterial cell walls and bacterial biofilms limits its antimicrobial activity. To overcome these limitations, we propose some formulations of MB based on different cationic liposomes. The liposome-MB systems were characterized using dynamic light scattering (DLS), zeta potential analysis and UV-visible spectroscopy. Their ability to penetrate inside the cytoplasm of E. coli, taken as a bacterial model for Gram-negative strains, was investigated through laser scanning confocal microscopy (CLSM) and compared to the penetration of naked MB. Then, MB-loaded liposomes were photo-activated and their antimicrobial activity was tested against E. coli, showing a strong improvement with respect to MB solutions. The liposomal formulations dramatically enhance MB penetration in bacterial biofilms and reduce the inflammatory response due to lipopolysaccharide exposure in mammalian cells. The observed antimicrobial and anti-inflammatory efficacies show a clear correlation with some structural features of the carriers, namely the size and the surface charge density. Overall, these results provide fundamental knowledge that enables the design of novel efficient PDT treatments, which potentially overcome the rising incidence of antibiotic resistance of bacterial strains.
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http://dx.doi.org/10.1039/c6tb03367aDOI Listing
April 2017

Catching anions with coloured assemblies: binding of pH indicators by a giant-size polyammonium macrocycle for anion naked-eye recognition.

Org Biomol Chem 2016 Sep 17;14(35):8309-21. Epub 2016 Aug 17.

Dipartimento di Chimica 'Ugo Schiff', Università degli Studi di Firenze, Via della Lastruccia 3, 50019, Sesto Fiorentino, Firenze, Italy.

A giant-size polyamine macrocycle L, composed of four 1,4,8,11-tetraazacyclotetradecane (cyclam) units linked by 1,3-dimethylenbenzyl spacers, strongly interacts in aqueous solution with four pH indicators (bromocresol purple (H2BCP), phenol red (H2PR), phenolphthalein (H2PP) and fluorescein (H2F)) in their anionic forms. Besides 1 : 1 complexes, L also forms assemblies with an unusual 1 : 2 receptor to dye stoichiometry, thanks to its large dimensions, which allow for the simultaneous interaction of the receptor protonated forms with two anionic dyes. The formation of the assemblies markedly affects the pKa values of the phenol groups of the dyes, which change colour upon complexation in well-defined pH ranges. This property can be effectively exploited for optical detection of anions. The L-H2BCP 1 : 2 assembly is able to selectively detect the triphosphate anion at slightly acidic pH values, thanks to the release, upon triphosphate coordination, of the dye from the ensemble, with a consequent colour change of the solution from purple-violet (complexed BCP(2-) dye) to yellow (free BCP(2-)). No effect is caused by other inorganic anions. The L-H2BCP 1 : 2 assembly represents a rare case of an optical chemosensor for the triphosphate anion.
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http://dx.doi.org/10.1039/c6ob01474gDOI Listing
September 2016

Reciprocal voltage sensor-to-pore coupling leads to potassium channel C-type inactivation.

Sci Rep 2016 06 9;6:27562. Epub 2016 Jun 9.

Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.

Voltage-gated potassium channels open at depolarized membrane voltages. A prolonged depolarization causes a rearrangement of the selectivity filter which terminates the conduction of ions - a process called slow or C-type inactivation. How structural rearrangements in the voltage-sensor domain (VSD) cause alteration in the selectivity filter, and vice versa, are not fully understood. We show that pulling the pore domain of the Shaker potassium channel towards the VSD by a Cd(2+) bridge accelerates C-type inactivation. Molecular dynamics simulations show that such pulling widens the selectivity filter and disrupts the K(+) coordination, a hallmark for C-type inactivation. An engineered Cd(2+) bridge within the VSD also affect C-type inactivation. Conversely, a pore domain mutation affects VSD gating-charge movement. Finally, C-type inactivation is caused by the concerted action of distant amino acid residues in the pore domain. All together, these data suggest a reciprocal communication between the pore domain and the VSD in the extracellular portion of the channel.
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http://dx.doi.org/10.1038/srep27562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899724PMC
June 2016

Adnexal localization of Crohn's disease and recurrent massive ovary cysts.

Rev Esp Enferm Dig 2016 Aug;108(8):525-6

General and Specialistic Surgery/4th Surgery, Città della Salute e della Scienza di Torino, Italy.

In a recent interesting case report, Saborit et al. reported three cases of ovarian involvement in Crohn's disease (CD). In the first two cases, there were pelvic abscesses due to fistulae of ileal loops affected by CD, with involvement of the right ovary, which also showed abscesses and typical granulomas. In the third case there was an ovarian abscess, extension of the process by contiguity. Granulomatous affectation of the ovaries is rare, with only 18 cases reported in the literature to date. Of this, in 17 cases the proposed mechanism of disease manifestation is direct fistulization between the small intestine and the ovary, which allows passage of vegetable material and results in the formation of reactive granulomas. In only one case a patient that did not demonstrate the histological features of either fistula-related disease (an intact ovarian capsule was found) or idiopathic granulomatous disease caused by the multiplicity of the granulomas and the presence of central necrosis has been reported. The authors therefore suggested that their findings were consistent with a diagnosis of metastatic CD of the ovary.
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http://dx.doi.org/10.17235/reed.2016.4301/2016DOI Listing
August 2016

Phosphate binding by a novel Zn(II) complex featuring a trans-1,2-diaminocyclohexane ligand. Effective anion recognition in water.

Org Biomol Chem 2015 Feb;13(6):1860-8

Dipartimento di Chimica "Ugo Schiff", Università di Firenze, Polo Scientifico e Tecnologico, I-50019 Sesto Fiorentino, Firenze, Italy.

In this work we have investigated the binding properties of a new synthetic receptor for phosphate anions that combines metal ion coordination with electrostatic and H-bonding interactions. The described receptor is obtained by assembling an iminodiacetic (IDA) fragment, as a Zn(II) binding site, with a polyamine macrocyclic portion containing two trans-1,2-diaminocyclohexane (DAC) units and a pyrrole ring, as a cationic binding site, into an adaptive structure appropriately spanning the length of di- and tridentate phosphates. Potentiometric measurements together with (1)H and (31)P NMR investigation showed that, in a wide pH range including values of physiological interest, the Zn(II) complex of the receptor binds di- and triphosphates, such as ADP, ATP, pyrophosphate (PP) and triphosphate (TP), far better than monophosphate (MP), and that TP is poorly bound by methyliminodiacetate (MIDA) as a model for the Zn(II) binding site. Besides the excellent selectivity over other phosphates, the affinity for TP is the largest reported to date for Zn(II) complexes in water.
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http://dx.doi.org/10.1039/c4ob02321hDOI Listing
February 2015

Microtransplantation of cellular membranes from squid stellate ganglion reveals ionotropic GABA receptors.

Biol Bull 2013 Feb;224(1):47-52

Grass Laboratory at the Marine Biological Laboratory, 7 MBL St., Woods Hole, MA 02543, USA.

The squid has been the most studied cephalopod, and it has served as a very useful model for investigating the events associated with nerve impulse generation and synaptic transmission. While the physiology of squid giant axons has been extensively studied, very little is known about the distribution and function of the neurotransmitters and receptors that mediate inhibitory transmission at the synapses. In this study we investigated whether γ-aminobutyric acid (GABA) activates neurotransmitter receptors in stellate ganglia membranes. To overcome the low abundance of GABA-like mRNAs in invertebrates and the low expression of GABA in cephalopods, we used a two-electrode voltage clamp technique to determine if Xenopus laevis oocytes injected with cell membranes from squid stellate ganglia responded to GABA. Using this method, membrane patches containing proteins and ion channels from the squid's stellate ganglion were incorporated into the surface of oocytes. We demonstrated that GABA activates membrane receptors in cellular membranes isolated from squid stellate ganglia. Using the same approach, we were able to record native glutamate-evoked currents. The squid's GABA receptors showed an EC(50) of 98 μmol l(-1) to GABA and were inhibited by zinc (IC(50) = 356 μmol l(-1)). Interestingly, GABA receptors from the squid were only partially blocked by bicuculline. These results indicate that the microtransplantation of native cell membranes is useful to identify and characterize scarce membrane proteins. Moreover, our data also support the role of GABA as an ionotropic neurotransmitter in cephalopods, acting through chloride-permeable membrane receptors.
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http://dx.doi.org/10.1086/BBLv224n1p47DOI Listing
February 2013