Transduction of selective recognition by preorganized ionophores, K+ selectivity of the different 1,3-diethoxycalix[4]arene crown ether conformers

Three different conformers of 1,3-diethoxy-p-tert-butylcalix[4]arene crown ethers have been used to study the effect of the ionophore preorganization on the potentiometric K+-selectivity. Selectivities were measured for chemically modified field effect transistors (CHEMFETs) and membrane ion-selective electrodes (ISEs) by two different methods. The ionophores show decreasing K+/Na+ selectivities in the order: partial cone > 1.3-alternate > cone. As a function of time the cone conformer maintained a constant selectivity whereas a continuous decrease of the selectivity values was observed for the other two conformers. This supports our prediction based on the association constants and our previous 1H NMR studies on conformational stability. \u

Glans dehiscence after severe hypospadias repair. Is it a real complication? Clues from a study in post-pubertal patients

Introduction: Glans dehiscence (GD) is reportedly a common complication after proximal hypospadias repairs. However, the need for surgical correction is controversial. The aim of this study was to assess awareness, risk factors, and outcome of GD in post-pubertal patients. The agreement with surgeon assessment was also evaluated. Methods: The design was retrospective. All consecutive patients treated for proximal hypospadias between 2000 and 2011 were included. The presence of GD was self-reported, and the participants could optionally upload a photograph for surgeon assessment. Cosmetic and functional outcomes were assessed by validated questionnaires (HOSE, PPPS, KINDL®, IIEF-5). Results were compared between patients with and without GD. Results: Of 219 patients, 34 (16%) participated. Fourteen of them (41%) self-reported GD. Eighteen patients (8%) also uploaded a photograph and, in ten of them (56%), the surgeon noted the presence of GD with poor agreement [k = - 0.444 (95 CI - 0.856 to - 0.033)] with patient report. Patients self-reporting GD had had more frequently a penile curvature at diagnosis (12/14 = 86%, p = 0.01), and had undergone a single-staged repair (100% vs. 65%, p = 0.03). No difference was found in cosmetic and functional outcomes. Results were similar also comparing groups with and without GD as assessed by the surgeon. Conclusion: GD was a common finding after severe hypospadias repair. It was more common in case of surgeon assessment with poor agreement between patients and surgeons. GD did not prove to have clear clinical implications. Therefore, in our opinion, surgical repair of GD should be recommended only on patients request

Synthesis of glycose carbamides and evaluation of the induction of erythroid differentiation of human erythroleukemic K562 cells

SUMMARY A series of carbamides derived from 1,2:5,6-di-O-isopropylidene-D-gluco- (1) and D-allofuranose (3) as well as their 5,6-O-deprotected analogues (2 and 4) and methyl 3,4-O-isopropylidene-alfa- and beta-D-galactopyranosides (5 and 6) have been prepared in order to evaluate their ability to induce erythroid differentiation of human erythroleukemic K562 cells. Twenty out of 51 carbamides tested exhibit an appreciable activity as inducers of erythroid differentiation and have been fully characterized and described

Novel Pyrrolidine Derivatives of Budesonide as Long Acting Inhaled Corticosteroids for the Treatment of Pulmonary Inflammatory Diseases

Inhaled corticosteroids (ICSs) represent the first line therapy for the treatment of asthma and are also extensively utilized in chronic obstructive pulmonary disease. Our goal was to develop a new ICS with a basic group, which can allow solid state feature modulation, achieving at the same time high local anti-inflammatory effect and low systemic exposure. Through a rational drug design approach, a new series of pyrrolidine derivatives of budesonide was identified. Within the series, several compounds showed nanomolar binding affinity (<i>K</i>_i) with GR that mostly correlated with the effect in inducing GR nuclear translocation in CHO cells and anti-inflammatory effects in macrophagic cell lines. Binding and functional cell-based assays allowed identifying compound <b>17</b> as a potent ICS agonist with a PK profile showing an adequate lung retention and low systemic exposure in vivo. Finally, compound <b>17</b> proved to be more potent than budesonide in a rat model of acute pulmonary inflammation