New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators

A series of histamine (HST)-related compounds were synthesized and tested for their activating properties on five physiologically relevant human Carbonic Anhydrase (hCA) isoforms (I, II, Va, VII and XIII). The imidazole ring of HST was replaced with different 5-membered heterocycles and the length of the aliphatic chain was varied. For the most interesting compounds some modifications on the terminal amino group were also performed. The most sensitive isoform to activation was hCA I (K(A) values in the low micromolar range), but surprisingly none of the new compounds displayed activity on hCA II. Some derivatives (1, 3a and 22) displayed an interesting selectivity for activating hCA I over hCA II, Va, VII and XIII

Agents with inotropic properties for the management of acute heart failure syndromes. Traditional agents and beyond

Treatment with inotropic agents is one of the most controversial topics in heart failure. Initial enthusiasm, based on strong pathophysiological rationale and apparent empirical efficacy, has been progressively limited by results of controlled trials and registries showing poorer outcomes of the patients on inotropic therapy. The use of these agents remains, however, potentially indicated in a significant proportion of patients with low cardiac output, peripheral hypoperfusion and end-organ dysfunction caused by heart failure. Limitations of inotropic therapy seem to be mainly related to their mechanisms of action entailing arrhythmogenesis, peripheral vasodilation, myocardial ischemia and damage, and possibly due to their use in patients without a clear indication, rather than to the general principle of inotropic therapy itself. This review will discuss the characteristics of the patients with a potential indication for inotropic therapy, the main data from registries and controlled trials, the mechanism of the untoward effects of these agents on outcomes and, lastly, perspectives with new agents with novel mechanisms of action

The packing of two species of polygons on the square lattice

We decorate the square lattice with two species of polygons under the constraint that every lattice edge is covered by only one polygon and every vertex is visited by both types of polygons. We end up with a 24 vertex model which is known in the literature as the fully packed double loop model. In the particular case in which the fugacities of the polygons are the same, the model admits an exact solution. The solution is obtained using coordinate Bethe ansatz and provides a closed expression for the free energy. In particular we find the free energy of the four colorings model and the double Hamiltonian walk and recover the known entropy of the Ice model. When both fugacities are set equal to two the model undergoes an infinite order phase transition.Comment: 21 pages, 4 figure

Lepton Flavor Violation in Supersymmetric SO(10) Grand Unified Models

The study for lepton flavor violation combined with the neutrino oscillation may provide more information about the lepton flavor structure of the grand unified theory. In this paper, we study two lepton flavor violation processes, $\tau\to \mu\gamma$ and $Z\to \tau\mu$, in the context of supersymmetric SO(10) grand unified models. We find the two processes are both of phenomenological interest. In particular the latter may be important in some supersymmetric parameter space where the former is suppressed. Thus, Z-dacay may offer another chance for looking for lepton flavor violation.Comment: 26 pages, 10 figure

Soft tissue sarcomas: introduction to the Virchows Archiv review issue

Molecular tumour pathology - and tumour genetic