Treatment of a compound calcaneus fracture Sanders IV with an external circular fixator and calcaneal osteotomy.

Compound Gustilo-type III intra-articular calcaneus fractures are challenging to treat. Anatomical reduction of the subtalar joint increases the chances of a better functional outcome and is traditionally achieved by an open reduction and plating. Conversely, ORIF is associated with a high risk of infection and even amputation.

Design of novel tripyridinophane-based Eu(III) complexes as efficient luminescent labels for bioassay applications.

In this work, the development of highly luminescent europium(III) complexes in water solution is reported, including their syntheses, analyses of their photophysical properties and applications in bioassays. Three Eu(III) complexes are derived from new ligands based on a tripyridinophane platform. There are four distinct sections in the structure of these ligands: an 18-membered polyaminocarboxylic macrocycle to bind efficiently lanthanide ions in aqueous solutions, three chromophoric subunits (4-(phenylethynyl)pyridine moieties) to effectively sensitize the emission of the metal, two peripheral moieties to solubilise the complex in aqueous media (sulfonate, sulfobetaine or glucose groups) and a free NH group available for grafting or bioconjugation.

Luminescent lanthanide complexes for reactive oxygen species biosensing and possible application in Alzheimer's diseases.

Histopathological hallmarks of Alzheimer's disease (AD) are intracellular neurofibrillary tangles and extracellular formation of senile plaques composed of the aggregated amyloid-beta peptide along with metal ions (copper, iron or zinc). In addition, oxidative stress is considered as an important factor in the etiology of AD and a multitude of metalloproteins and transporters is affected, leading to metal ion misregulation. Redox-active metal ions (e.

Tripyridinophane Platform Containing Three Acetate Pendant Arms: An Attractive Structural Entry for the Development of Neutral Eu(III) and Tb(III) Complexes in Aqueous Solution.

We report a detailed characterization of Eu and Tb complexes derived from a tripyridinophane macrocycle bearing three acetate side arms (Htpptac). Tpptac displays an overall basicity (∑ log ) of 24.5, provides the formation of mononuclear ML species, and shows a good binding affinity for Ln (log = 17.

New polyaminocarboxylate macrocycles containing phenolate binding units: synthesis, luminescent and relaxometric properties of their lanthanide complexes.

The synthesis of two new polyaminocarboxylate macrocycles incorporating one or two intracyclic phenol units (HL and HL, respectively) is described. The 12-membered HL macrocycle leads to soluble and stable mononuclear Ln complexes of [(L)Ln(HO)] composition (Ln = Eu, Tb and Gd) in aqueous solutions. In Tris buffer (pH 7.

Optical and relaxometric properties of monometallic (Eu(III), Tb(III), Gd(III)) and heterobimetallic (Re(I)/Gd(III)) systems based on a functionalized bipyridine-containing acyclic ligand.

A series of lanthanide complexes of [LnL(H2O)](2-) composition where Ln = Eu(III), Tb(III) or Gd(III) has been studied for determining their photophysical and relaxometric properties in aqueous solution. The bifunctional ligand L (H5BPMNTA) is an acyclic chelator based on a central functionalized 2,2'-bipyridine core and two iminodiacetate coordinating arms. The mono-aqua Eu(III) and Tb(III) complexes display attractive spectroscopic properties with an excitation wavelength at 316 nm, similar excited state lifetimes and overall quantum yields (in the ranges 0.

Terpyridine-based heteroditopic ligand for Ru(II)Ln3(III) metallostar architectures (Ln = Gd, Eu, Nd, Yb) with MRI/optical or dual-optical responses.

A new ditopic ligand (L) based on a 2,2':5',4″-terpyridine unit substituted in the 2″,6″ positions with iminodiacetate arms has been designed and synthesized for the construction of Ru(II)L3Ln3(III) supramolecular architectures. The two components of this system, a 2,2'-bipyridine unit for Ru(II) coordination and a pyridine-bis(iminodiacetate) core for Ln(III) coordination, are tightly connected via a covalent Carom(py)-Carom(py) bond. The paramagnetic and photophysical properties of the corresponding tetrametallic Ru(II)L3Gd3(III) complex have been evaluated, highlighting the potential of this metallostar structure to act as a bimodal MRI/optical imaging agent.

Bifunctional Gd(III) and Tb(III) chelates based on a pyridine-bis(iminodiacetate) platform, suitable optical probes and contrast agents for magnetic resonance imaging.

To study the physicochemical properties of lanthanide complexes derived from a bifunctional chelating agent based on a PMN-tetraacetic acid moiety {PMN-tetraacetic acid (1): [2,6-pyridinediylbis(methylene nitrilo)-tetraacetic acid]}, 4-carboxylic acid substituted pyridine derivative (2) was synthesized. This ligand forms heptadentate (N3 O4 ) Ln(III) complexes (Ln = Gd, Eu, Tb), with two water molecules completing the inner coordination sphere of the metal. The parameters that govern the relaxivity of the Gd(III) complex and the luminescence of Eu(III) and Tb(III) complexes were obtained by (17) O and (1) H NMR studies and time-resolved fluorescence experiments, respectively.

Synthesis and preliminary biological evaluation of the first (99m)Tc(I)-specific semi-rigid tridentate ligand based on a click chemistry strategy.

A novel bifunctional chelating agent based on a click chemistry strategy has been synthesized and characterized on the basis of spectroscopic techniques. The metal chelating part of this new class of tridentate N2O ligand combined a triazole unit and an aromatic ring. This latter semi-rigid framework induced a pre-organization of the chelating cavity, improving the stability of the corresponding metallic complexes (M = (99m) Tc, Re).

A functionalized heterobimetallic (99m)Tc/Re complex as a potential dual-modality imaging probe: synthesis, photophysical properties, cytotoxicity and cellular imaging investigations.

A novel bimodal fluorescent/radiolabelled probe based on a pyridyltriazole scaffold (known as pyta) is reported here. The final dual imaging agent combines carboxylate functionalization, for biomolecule conjugation, with two distinct metal chelating sites: a pyta-based tricarbonylrhenium moiety as a fluorescent probe and a (99m)Tc(CO3)(+) core through the tridentate chelating iminodiacetic acid (IDA) clamp as a SPECT reporter. The heterodinuclear (99m)Tc/Re complex , as well as its non-radioactive dirhenium analog , was prepared in six steps.

Bilateral stereotactic anterior capsulotomy for obsessive-compulsive disorder: long-term follow-up.

Background And Purpose: Psychosurgery, such as anterior capsulotomy, is a therapeutic option for treatment-resistant obsessive-compulsive disorder (OCD). In this paper, we present a prospective, long-term follow-up study aimed at evaluating both the efficacy and the safety of anterior capsulotomy for the treatment of severe, refractory OCD.

Methods: Twenty-four patients were surgically treated in our centre between 1997 and 2009, 19 of whom were included in this study.

Tricarbonylrhenium complexes from 2-pyridyl-1,2,3-triazole ligands bearing a 4-substituted phenyl arm: a combined experimental and theoretical study.

Three new pyridyltriazole ligands (named pyta) bearing a 4-substituted phenyl arm (nitro- (2a), chloro- (2b) or aminophenyl (2c) moiety) have been synthesized using a convenient click chemistry strategy. The corresponding tricarbonylrhenium complexes 3a, 3b and 3c were prepared and fully characterized by means of NMR, IR and mass spectrometry, as well as X-ray crystallography for two of them (3a and 3b). The direct connection of a 4-substituted phenyl arm at the N1 position of the triazolyl ring has a significant influence on the geometry of both, the ligands and their corresponding Re-complexes.

Di-tert-butyl N-{[1-(pyridin-4-yl)-1H-1,2,3-triazol-4-yl]methyl}iminodiacetate.

In the title compound, C(20)H(29)N(5)O(4), the pyridine ring makes a dihedral angle of 10.41 (16)° with the triazole ring, which exhibits an azo-like character. In the crystal, mol-ecules are linked by C-H⋯O and C-H⋯N hydrogen bonds, and C-H⋯π inter-actions involving a methyl group and the pyridine ring of a neighbouring mol-ecule, leading to the formation of a three-dimensional network.

Synthesis and optical properties of macrocyclic lanthanide(III) chelates as new reagents for luminescent biolabeling.

The convenient and efficient synthesis of two macrocyclic ligands (15- and 18-membered) based on a dipyrido-6,7,8,9-tetrahydrophenazine (dpqc) or 2,2':6',2''-terpyridine (tpy) heterocycle and a DTTA (diethylenetriaminetriacetic acid) skeleton is described. In these ligands the DTTA skeleton contains an additional extracyclic functionality (NH(2) group) suitable for covalent attachment to bioactive molecules. These octa- and nonadentate ligands form very stable and luminescent neutral lanthanide complexes in aqueous solutions at physiological pH.

Lanthanide(III) complexes of pyridine-tetraacetic acid-glycoconjugates: synthesis and luminescence studies of mono and divalent derivatives.

A potent lanthanide chelate, fulfilling the requirements for the development of MRI contrast agents or luminescent probes, was armed with alkyne groups. We then implemented a click methodology to graft the bifunctional ligand to azide-containing glucoside and maltoside scaffolds. The resulting hydrophilic glycoconjugates retained the ligand binding capacity for Eu(3+) or Tb(3+) ion as evidenced by the number of bound water molecules to the lanthanide ion.

First dinuclear Re/Tc complex as a potential bimodal Optical/SPECT molecular imaging agent.

In this communication, a novel synthetic pathway has been applied to prepare a dual imaging agent in a single molecule. The dinuclear Re(I)/Tc(I) complex 6, namely [Re(CO)(3)(bipy){(4-PyrIDA)Tc(CO)(3)}], is the first example of a Re/Tc-based heterometallic assembly which could act as a potential bimodal Optical/SPECT probe. Interestingly, the Re(I) complex intermediate 4 exhibits significant photophysical properties for biological applications.

Breast and ovarian cancer screening of non-carriers from BRCA1/2 mutation-positive families: 2-year follow-up of cohorts from France and Quebec.

We described and compared breast and ovarian screening practices in the 2-year period following test result disclosure in female non-carriers from BRCA1/2 mutation-positive families living in two countries, France and Quebec, Canada, which provide universal health care. Four hundred and two (France n=293; Quebec n=109) unaffected female non-carriers from BRCA-proven mutation families provided information about the uptake of mammography, clinical breast examination, breast self-examination, and ovarian ultrasounds using self-administered questionnaires. The frequency of screening practices between study cohorts were compared using logistic regression.

A click procedure with heterogeneous copper to tether technetium-99m chelating agents and rhenium complexes. Evaluation of the chelating properties and biodistribution of the new radiolabelled glucose conjugates.

An efficient protocol was developed to tether chelating agents and rhenium complexes onto a glucoside scaffold with a heterogeneous copper catalyst via click chemistry. The supported catalyst avoids the formation of unwanted copper complexes during the cyclisation step. The possibility to graft a pre-chelated M(CO)(3) core by click chemistry onto a biomolecule was highlighted for the first time.

Development of a new radioligand for cholecystokinin receptor subtype 2 scintigraphy: from molecular modeling to in vivo evaluation.

To improve the targeting to tumors expressing the cholecystokinin receptor subtype 2 (CCK2R) with limited kidney uptake, we synthesized a novel cholecystokinin C-terminal tetrapeptide (CCK4)-based derivative conjugated to an original bipyridine-chelator (BPCA), 111In-BPCA-(Ahx)2-CCK4. To our knowledge this is the first CCK4-based radioligand that presents a high affinity for the CCK2R, a high and specific tumor uptake, a low renal accumulation and a very good visualization of tumors in vivo compared with an internal control, 111Indium-trans-cyclohexyldiethylenetriaminepenta-acetic acid-cholecystokinin octapeptide (111In-CHX-A''-DTPA-CCK8). These properties make 111In-BPCA-(Ahx)2-CCK4, a promising candidate for imaging and peptide receptor radionuclide therapy of CCK2R positive tumors.

Synthesis, characterization and in vitro evaluation of new oxorhenium- and oxotechnetium-CCK4 derivatives as molecular imaging agents for CCK2-receptor targeting.

The goal of this study is to design new (99m)Tc-radiolabelled shortened CCK derivatives that might be suitable for the molecular imaging of cholecystokinin-2 receptors (CCK2-R), these receptors being over-expressed in a number of neuroendocrine tumors such as medullary thyroid cancer and small-cell lung cancer. For this purpose, we designed several modified CCK4 analogs bearing an ON(2)S tetradentate chelating agent at the N-terminus, the CCK4 sequence representing the minimal peptide sequence that presents nanomolar affinity and activity towards the CCK2-R. Four peptide conjugates of general formula (Trt)SN(2)OPh-(X)(n)-CCK4 (X=beta-alanine or 6-aminohexanoic acid spacers; n=0, 2, 4) and their oxorhenium peptide conjugates have been synthesized and characterized.

A dual lanthanide probe suitable for optical (Tb3+ luminescence) and magnetic resonance imaging (Gd3+ relaxometry).

A new polyaminocarboxylate ligand derived from N,C-pyrazolylpyridine was synthesized. The luminescence and relaxometry properties of its Tb(3+) and Gd(3+) chelates were investigated in aqueous solutions. The Tb(3+) chelate is strongly luminescent having remarkable lifetime and quantum yield (tau=1.

Bimodal system (luminophore and paramagnetic contrastophore) derived from Ln(III) complexes based on a bipyridine-containing macrocyclic ligand.

The synthesis of a new 15-membered polyaza-macrocyclic ligand L3H3, which is based on a 2,2'-bipyridine moiety and a diethylenetriaminetriacetic acid core, is reported. The lanthanide chelates of this octadentate ligand were programmed for bimodal probes, luminescent agents (Sm, Eu, Tb, Dy), and magnetic resonance imaging agents (Gd3+). The neutral 1:1 complexes with these Ln3+ ions were prepared and studied in aqueous solution by luminescence and NMR techniques.

Direct access to terpyridine-containing polyazamacrocycles as photosensitizing ligands for Eu(III) luminescence in aqueous media.

[reaction: see text] The synthesis of new 18-membered hexaazamacrocycles containing a functionalized 2,2':6',2' '-terpyridine moiety as part of the cyclic backbone and three acetate pendant arms is described. The reported synthetic procedure is based on the use of an efficient metal template ion effect which controls the macrocyclization step. This procedure is compatible with some functional groups present in the macrocyclic structure.