Structural Aspects of Palladium Systems Used as Catalyst Precursors in CO/olefins co- and ter-Polymerisation Reactions

The synthesis and characterisation of three palladium complexes, involved in the homogeneous catalysis towards the CO-olefins co-and ter-polymerisation reactions, are reported. The [Pd (dpk⋅CH3OH) (CF3CO2)2] (1), (dpk = di(2-pyridyl) ketone) and [Pd (dppp)(bipy)] [B(C6F5)4]2 (2), (bipy = 2,2’-bipyridine, dppp = 1,3-bis(diphenylphosphino)propane) compounds are examples of a neutral complex and of a dicationic mixed-ligands one, respectively. The catalytic activity of type 2 complexes was reported to be strongly dependent on the nature of the anion, and the tetra(perfluorophenyl) borate salt represents the best choice to date for the CO/aliphatic olefins copolymerisation. In both structures, the metal has a square planar coordination and the structural aspects of these complexes are discussed in comparison with their catalytic properties. The crystal structure of [Pd(bipy)(naphthoquinone)] (3), which is a putative intermediate of the catalytic cycle, is also reported

Structural Aspects of Palladium Systems Used as Catalyst Precursors in CO/olefins co- and ter-Polymerisation Reactions

The synthesis and characterisation of three palladium complexes, involved in the homogeneous catalysis towards the CO-olefins co-and ter-polymerisation reactions, are reported. The [Pd (dpk⋅CH3OH) (CF3CO2)2] (1), (dpk = di(2-pyridyl) ketone) and [Pd (dppp)(bipy)] [B(C6F5)4]2 (2), (bipy = 2,2’-bipyridine, dppp = 1,3-bis(diphenylphosphino)propane) compounds are examples of a neutral complex and of a dicationic mixed-ligands one, respectively. The catalytic activity of type 2 complexes was reported to be strongly dependent on the nature of the anion, and the tetra(perfluorophenyl) borate salt represents the best choice to date for the CO/aliphatic olefins copolymerisation. In both structures, the metal has a square planar coordination and the structural aspects of these complexes are discussed in comparison with their catalytic properties. The crystal structure of [Pd(bipy)(naphthoquinone)] (3), which is a putative intermediate of the catalytic cycle, is also reported

Cardiomyopathy, familial dilated

Dilated cardiomyopathy (DCM) is a heart muscle disease characterized by ventricular dilatation and impaired systolic function. Patients with DCM suffer from heart failure, arrhythmia, and are at risk of premature death. DCM has a prevalence of one case out of 2500 individuals with an incidence of 7/100,000/year (but may be under diagnosed). In many cases the disease is inherited and is termed familial DCM (FDC). FDC may account for 20–48% of DCM. FDC is principally caused by genetic mutations in FDC genes that encode for cytoskeletal and sarcomeric proteins in the cardiac myocyte. Family history analysis is an important tool for identifying families affected by FDC. Standard criteria for evaluating FDC families have been published and the use of such criteria is increasing. Clinical genetic testing has been developed for some FDC genes and will be increasingly utilized for evaluating FDC families. Through the use of family screening by pedigree analysis and/or genetic testing, it is possible to identify patients at earlier, or even presymptomatic stages of their disease. This presents an opportunity to invoke lifestyle changes and to provide pharmacological therapy earlier in the course of disease. Genetic counseling is used to identify additional asymptomatic family members who are at risk of developing symptoms, allowing for regular screening of these individuals. The management of FDC focuses on limiting the progression of heart failure and controlling arrhythmia, and is based on currently accepted treatment guidelines for DCM. It includes general measures (salt and fluid restriction, treatment of hypertension, limitation of alcohol intake, control of body weight, moderate exercise) and pharmacotherapy. Cardiac resynchronization, implantable cardioverter defibrillators and left ventricular assist devices have progressively expanding usage. Patients with severe heart failure, severe reduction of the functional capacity and depressed left ventricular ejection fraction have a low survival rate and may require heart transplant

Water-Soluble Ruthenium(III)-Dimethyl Sulfoxide Complexes: Chemical Behaviour and Pharmaceutical Properties

In this paper we report a review of the results obtained in the last few years by our group in the development of ruthenium(III) complexes characterized by the presence of sulfoxide ligands and endowed with antitumor properties. In particular, we will focus on ruthenates of general formula Na[trans-RuCl4(R1R2SO)(L)], where R1R2SO = dimethylsulfoxide (DMSO) or tetramethylenesulfoxide (TMSO) and L = nitrogen donor ligand. The chemical behavior of these complexes has been studied by means of spectroscopic techniques both in slightly acidic distilled water and in phosphate buffered solution at physiological pH. The influence of biological reductants on the chemical behavior is also described. The antitumor properties have been investigated on a number of experimental tumors. Out of the effects observed, notheworthy appears the capability of the tested ruthenates to control the metastatic dissemination of solid metastasizing tumors. The analysis of the antimetastatic action, made in particular on the MCa mammary carcinoma of CBA mouse, has demonstrated a therapeutic value for these complexes which are able to significantly prolong the survival time of the treated animals. The antimetastatic effect is not attributable to a specific cytotoxicity for metastatic tumor cells although in vitro experiments on pBR322 double stranded DNA has shown that the test ruthenates bind to the macromolecule, causing breaks corresponding to almost all bases, except than thymine, and are able to cause interstrand bonds, depending on the nature of the complex being tested, some of which results active as cisplatin itself

AFM macro-probes to investigate whole 3D cardiac spheroids

In its many applications, the Atomic Force Microscope (AFM) is a promising tool in cardiac mechanobiology because it can unravel the viscoelastic and mechano-dynamic properties of individual cardiomyocytes. However, the biophysical investigation of more accurate 3D models is hampered by commercial probes, which typically operate at the cell sub-compartmental resolution. We have previously shown how flat macro-probes can overcome these limitations by extending the AFM mechanical measurements to multicellular aggregates. Such macro-probes are fabricated by standard micromachining and carry a flat polymeric wedge to offset the AFM mounting tilt. Therefore, the AFM is upgraded to a micro-parallel plate rheometer with unmatched force range and sensitivity. In this article, we show how these macro-probes can be applied to reveal the global rheology of primary cardiomyocytes spheroids, by performing stress-relaxation tests. More importantly, we demonstrate that these macro-probes can be used as passive sensors capable of monitoring the spheroid beating force and beating pattern, and to perform a “micro-CPR” on the spheroid itself

Molecular and Cellular Mechanisms in Heart Failure

Pathophysiology and treatment of pediatric heart failure (HF) is poorly understood. A growing body of literature demonstrates age-related differences in mechanisms and in therapies efficacy. HF results from ventricular dysfunction due to volume or/and pressure overload. Circulatory, neurohormonal, and molecular alterations promote the progression of HF and ventricular remodeling; they include inflammation, oxidative stress, mitochondrial dysfunction, loss of cardiomyocytes, and fibrosis. Children and young affected by cardiomyopathies have the greatest risk of HF and heart transplantation. Genetic mutations of sarcomere, cytoskeleton, cell membrane proteins, and ion channels have been recognized as the main causes of many cardiomyopathy phenotypes. In particular, sarcomeric and cytoskeleton genes mutations seem to have an important role in the progression of HF. Prognostic stratification and clinical management could benefit from identification of biomarkers such as inflammatory mediators or microRNA (miRNA). miRNA and myocardial regenerative strategies are under investigations as potential novel therapeutic approaches

Reduction of Lung Metastases by Na[trans-RuCl4(DMSO)Im] is not Coupled With the Induction of Chemical Xenogenization

The effects of the treatment of tumor cells of MCa mammary carcinoma and TLX5 lymphoma with the ruthenium complex Na[trans-RuCl4 (DMSO)lm] for several transplant generations were studied on tumor growth and metastases formation. On TLX5 lymphoma cells, treatment was performed in vitro prior to in vivo inoculation of tumor cells in intact or immunesuppressed mice. Either considering tumor take and growth or its capacity to invade the brain of the inoculated hosts, Na[trans-RuCl4(DMSO)lm] did not induce any significant modification. Conversely, in mice with MCa mammary carcinoma, the in vivo treatment of tumor cells in immunesuppressed hosts caused a progressive increase of DNA activity and, starting from the 4th transplant generation, a significantly increased susceptibility of lung metastasis formation to a further treatment in intact mice. These data seem to suggest that Na[trans-RuCl4(DMSO)Im] does not induce chemical xenogenization of tumor cells nor its repeated treatment induces resistance in tumor cells. Conversely, it appears that Na[trans-RuCl4(DMSO)lm] may select a tumor cell population which maintains its capacity to metastasise to the lung but with enhanced sensitivity to the antimetastatic properties of this compound

Efficacy of 5-FU Combined to Na[trans-RuCl4(DMSO)Im], A Novel Selective Antimetastatic Agent, on the Survival Time of Mice With P388 Leukemia, P388/DDP subline and MCa Mammary Carcinoma

The combinational treatment between the selective antimetastatic agent, sodium-trans-rutheniumtetrachloridedimethylsulfoxideimidazole, Na[trans-RuCl4(DMSO)Im], and the cytotoxic drug 5-fluorouracil (5-FU) on primary tumor growth and on the survival time of experimental tumors results in an effect significantly greater than that of each single agent used alone either with the solid metastasizing MCa mammary carcinoma of the CBA mouse or with the lymphocytic leukemia P388 and its platinum resistant P388/DDP subline. Thus the inorganic compound Na[trans-RuCl4(DMSO)Im], known for its potent and selective antimetastatic effects, positively interacts with the antitumor action of an organic anticancer agent such as 5-FU on both a solid metastasizing tumor and a tumor of lymphoproliferative type. In particular, the effects of the combinational treatment on the survival time of tumor bearing mice seem to be related to the selective antimetastatic activity of the ruthenium complex that joins the potent cytotoxicity of 5-FU for the tumor. Moreover, these data show that Na[trans-RuCl4(DMSO)Im] is almost as effective on the subline of P388 made resistant to cisplatin as it was on the parental line

Sex differences in natural history of cardiovascular magnetic resonance- and biopsy-proven lymphocytic myocarditis

Aims: the role of sex in determining the profile and the outcomes of patients with myocarditis is largely unexplored. We evaluated the impact of sex as a modifier factor in the clinical characterization and natural history of patients with definite diagnosis of myocarditis. Methods and results: we retrospectively analysed a single-centre cohort of consecutive patients with definite diagnosis of myocarditis (i.e. endomyocardial biopsy or cardiac magnetic resonance proven). Specific sub-analyses were performed in cohorts of patients with chest pain, ventricular arrhythmias, and heart failure as different main symptoms at presentation. The primary outcome measure was a composite of all-cause mortality or heart transplantation (HTx). We included 312 patients, of which 211, 68% of the whole population, were males. Despite no clinically relevant differences found at baseline presentation, males had a higher indexed left ventricular end-diastolic volume (62 ± 23 mL/m2 vs. 52 ± 20 mL/m2, P = 0.011 in males vs. females, respectively) at follow-up evaluation. At a median follow-up of 72 months, 36 (17%) males vs. 8 (8%) females experienced death or HTx (P = 0.033). Male sex emerged as predictors of all-cause mortality or HTx in every combination of covariates (HR 2.600; 1.163–5.809; P = 0.020). Results were agreeable regardless of the main symptom of presentation. Conclusions: in a large cohort of patients with definite diagnosis of myocarditis, females experienced a more favourable long-term prognosis than males, despite a similar clinical profile at presentation

Natural History of Dilated Cardiomyopathy in Children

The long-term progression of idiopathic dilated cardiomyopathy (DCM) in pediatric patients compared with adult patients has not been previously characterized. In this study, we compared outcome and long-term progression of pediatric and adult DCM populations