Long-Term Evolution and Prognostic Stratification of Biopsy-Proven Active Myocarditis

Background— Active myocarditis is characterized by large heterogeneity of clinical presentation and evolution. This study describes the characteristics and the long-term evolution of a large sample of patients with biopsy-proven active myocarditis, looking for accessible and valid early predictors of long-term prognosis. Methods and Results— From 1981 to 2009, 82 patients with biopsy-proven active myocarditis were consecutively enrolled and followed-up for 147±107 months. All patients underwent clinical and echocardiographic evaluation at baseline and at 6 months. At this time, improvement/normality of left ventricular ejection fraction (LVEF), defined as a LVEF increase > 20 percentage points or presence of LVEF≥50%, was assessed. At baseline, left ventricular dysfunction (LVEF<50%) and left atrium enlargement were independently associated with long-term heart transplantation–free survival, regardless of the clinical pattern of disease onset. At 6 months, improvement/normality of LVEF was observed in 53% of patients. Persistence of New York Heart Association III to IV classes, left atrium enlargement, and improvement/normality of LVEF at 6 months emerged as independent predictors of long-term outcome. Notably, the short-term reevaluation showed a significant incremental prognostic value in comparison with the baseline evaluation (baseline model versus 6 months model: area under the curve 0.79 versus 0.90, P =0.03). Conclusions— Baseline left ventricular function is a marker for prognosis regardless of the clinical pattern of disease onset, and its reassessment at 6 months appears useful for assessing longer-term outcome

Characterization of persistent intramolecular C-H⋅⋅⋅X(N,O) bonds in solid state and solution

The formation of intramolecular CH⋅⋅⋅X(N,O) bonds and their persistence in solution were studied by X-ray crystallography and NMR techniques in two different rotamers of a molecule containing the ortho-carborane cage, an amide group and a quinoline ring. Experimental data were confirmed by theoretical ab initio calculations. From the resolved structure of the two forms of this potentially active drug for boron neutron capture therapy, accurate bonding and geometric parameters were extracted for this non-classic hydrogen interaction, and their strength was calculated. These findings provided new insight in the theory of CH⋅⋅⋅X bonds, which appear stronger and less rare than it was previously thought

Miocardite: la grande simulatrice

Myocarditis is a rare, but life threatening disease in childhood. It is most often due to common viral infections; less commonly, it may result from bacterial infections, immune mediated diseases or chemotherapy. Myocarditis may present with unspecific symptoms, ranging from respiratory to gastrointestinal ones; a clear hypomobility is the typical sign of myocarditis (\u201cthe immobile child\u201d). The diagnosis is based on electrocardiogram and echocardiography, which are always pathologic but unspecific; an X-chest is useful to identify cardiomegaly. Among laboratory tests, the most sensitive element is an increased level of aspartate aminotransferase, while troponin dosage has low specificity and not absolute sensitivity. Endomyocardial biopsy is the gold standard diagnostic test, but it should be performed only in patients who do not respond to usual treatment, because of the high risk of side effects. The mainstay of therapy is supportive therapy for left ventricular dysfunction. The fulminant viral forms usually have initial significant cardiovascular impairment, followed by a complete resolution. On the other hand, a subacute disease might have less initial cardiovascular impairment, but more often can evolve to chronic dilated cardiomyopathy. In this case immunosuppressive therapy could be useful

Enantioresolution and stereochemical characterization of two chiral sulfoxides endowed with COX-2 inhibitory activity

7nononenoneSardella, Roccaldo; Ianni, Federica; Michele, Alessandro Di; Capua, Angela Di; Carotti, Andrea; Anzini, Maurizio; Natalini, BenedettoSardella, Roccaldo; Ianni, Federica; Michele, Alessandro Di; Capua, Angela Di; Carotti, Andrea; Anzini, Maurizio; Natalini, Benedett

Molecular Structure and Dynamics of Some Potent 5-HT3 Receptor Antagonists. Insight into the Interaction with the Receptor

The molecular structure and the dynamic behaviour of some potent 5-HT3 antagonists structurally related to quipazine have been investigated by NMR spectroscopy and by computational methods in order to gain insight into the structure-activity relationships at a molecular level. The role of the different dynamic behaviour of these compounds in the binding to 5-HT3 receptors is discussed. A model of ligand-receptor interaction has been developed on the basis of molecular orbital calculations and on the reference ligands quipazine, ondansetron and LY278584. The interaction model proposed herein rationalizes the observed agonist-antagonist shift between quipazine and investigated compounds with the assumption of different but overlapping binding domains for antagonists and agonists at the 5-HT3 receptor. Copyrigh

Dendrimeric tetravalent ligands for the serotonin-gated ion channel

Multivalency is widely used in nature in specific recognition processes. This paper describes an approach to multivalency in the pentameric 5-HT 3 receptor, a ligand-gated ion channel, which constitutes an example of intrinsically multivalent biological receptors. Owing to the picomolar K i value, TETRA-L represents an outstanding multivalent ligand for the neurotransmitter receptor