Comparing the Prevalence of Polypharmacy and Potential Drug-Drug Interactions in Nursing Homes and in the Community Dwelling Elderly of Emilia Romagna Region.

We aimed at assessing the prevalence of polypharmacy and potential drug-drug interactions (DDIs) with clinical relevance in elderly patient on Emilia Romagna area. Both outpatients and residents in nursing homes were assessed, with only partially overlapping strategies. We defined a list of 190 pairs of potentially interacting drugs, based on literature appraisal and availability of therapeutic alternatives.

Dibenzoate esters of cis-tetralin-2,3-diol as analogs of (-)-epigallocatechin gallate: synthesis and crystal structure of anticancer drug candidates.

(-)-Epigallocatechin gallate (EGCG), the main component of green tea extract, displays multiple biological activities. However, it cannot be used as a drug due to its low cellular absorption, instability and metabolic degradation. Therefore, there is a need to provide analogs that can overcome the limitations of EGCG.

Antibacterial green tea catechins from a molecular perspective: mechanisms of action and structure-activity relationships.

This review summarizes the mechanisms of antibacterial action of green tea catechins, discussing the structure-activity relationship (SAR) studies for each mechanism. The antibacterial activity of green tea catechins results from a variety of mechanisms that can be broadly classified into the following groups: (1) inhibition of virulence factors (toxins and extracellular matrix); (2) cell wall and cell membrane disruption; (3) inhibition of intracellular enzymes; (4) oxidative stress; (5) DNA damage; and (6) iron chelation. These mechanisms operate simultaneously with relative importance differing among bacterial strains.

Determination of the absolute configuration of conformationally flexible molecules by simulation of chiro-optical spectra: a case study.

The assignment of the absolute configuration (AC) of two conformational flexible organic molecules by means of TD-DFT simulation of the electronic circular dichroism (ECD) spectra is presented. The factors leading to a reliable assignment were evaluated in the various steps of the process. The effects of different functionals and basis sets in the geometry optimization step is very limited in terms of the resulting optimized geometries, whereas the inclusion of the solvent in the calculations has a much larger effect on the correct evaluation of the conformational ratio.

Synthesis of Phthalides and α,β-butenolides by Transition Metal-Catalyzed Activation of C-H Bonds.

Phthalides and α,β-butenolides are two related classes of oxygenated heterocycles with a wide range of biological activities. An innovative strategy to prepare these compounds is based on C-H bond functionalization reactions, in which two simple, unfunctionalized molecules are coupled together with cleavage of a C-H bond and formation of a C-X bond (X=C or heteroatom). This paper reviews the methods for the synthesis of phthalides and α,β-butenolides by C-H bond functionalization from non-halogenated starting materials.

Corrigendum: Virulence Factor A2 Protein: Linear B-Cell Epitope Mapping and Identification of Three Main Linear B-Cell Epitopes in Vaccinated and Naturally Infected Dogs.

[This corrects the article DOI: 10.3389/fimmu.2018.

Virulence Factor A2 Protein: Linear B-Cell Epitope Mapping and Identification of Three Main Linear B-Cell Epitopes in Vaccinated and Naturally Infected Dogs.

In Brazil, canine visceral leishmaniasis (CVL) is caused by Leishmania infantum, presenting a broad spectrum of clinical manifestations. Dogs are the main parasite reservoir in urban areas and canine cases precede human infection. Currently, A2 protein based Leish-Tec® vaccine is the only vaccine commercially available against CVL in Brazil.

Biological and Mechanistic Characterization of Novel Prodrugs of Green Tea Polyphenol Epigallocatechin Gallate Analogs in Human Leiomyoma Cell Lines.

Uterine fibroids (leiomyomas) are very common benign tumors grown on the smooth muscle layer of the uterus, present in up to 75% of reproductive-age women and causing significant morbidity in a subset of this population. Although the etiology and biology of uterine fibroids are unclear, strong evidence supports that cell proliferation, angiogenesis and fibrosis are involved in their formation and growth. Currently the only cure for uterine fibroids is hysterectomy; the available alternative therapies have limitations.

Diastereomer Interconversion via Enolization: A Case Study.

The three-component reaction of indole, isobutyraldehyde, and methyl acetoacetate affords methyl 2-(acetyl)-3-(1H-indol-3-yl)-4-methylpentanoate as a single diastereomer. To investigate the origin of the observed diastereoselectivity, the thermodynamics and kinetics of interconversion of diastereomers 1 and 2 in solution were studied by a combination of (1)H nuclear magnetic resonance (NMR) spectroscopy, high-performance liquid chromatography (HPLC), mass spectrometry, and deuteration experiments. The results indicate that interconversion is both acid- and base-catalyzed, and that the alpha carbon is the only stereolabile center in the molecule.

TiCl4-promoted condensation of methyl acetoacetate, isobutyraldehyde, and indole: a theoretical and experimental study.

The mechanism of the TiCl4-promoted condensation of methyl acetoacetate, isobutyraldehyde, and indole was studied by a combination of theoretical and experimental techniques. The energy profile of plausible reaction paths was evaluated by DFT calculations, and various reaction intermediates were isolated or observed in solution by NMR spectroscopy. Theoretical and experimental results indicate that the reaction proceeds in three steps, all promoted by titanium: (1) formation of the enolate ion of methyl acetoacetate, (2) Knoevenagel condensation of the enolate ion and aldehyde, and (3) Michael addition of indole to the Knoevenagel adduct.

The persistence of allergen exposure favors pulmonary function decline in workers with allergic occupational asthma.

Background: In asthmatics, a rapid decline in pulmonary function is observed, likely as a consequence of airways remodeling. Persistence of allergen exposure in patients with occupational asthma (OA) maintains chronic bronchial inflammation, resulting in a more severe lung function decline. Few studies were performed on the effects of allergen exposure cessation.

Environmental pollution and asthma.

Clinical evidences and epidemiological studies show that allergic pathologies of the respiratory tract are increasing in the world areas with high pollution impact, demonstrating how many polluting substances favor both allergic sensitization and the bronchial inflammatory changes characteristic of asthma. It has been shown that asthma, as many other diseases, is a complex interaction between genetic predisposition and environmental stimuli that results in clinical expression of various phenotypes of asthma: allergic, intrinsic etc. Many pollutants have such a potential.

Maintenance venom immunotherapy administered at a 3-month interval preserves safety and efficacy and improves adherence.

Background: Hymenoptera venom immunotherapy (VIT) is a safe and effective approach to insect sting allergy. However, after discontinuation, relapses can occur in some patients, especially those with a high occupational risk, and they may need to prolong VIT indefinitely. In order to improve adherence, we propose extending the interval between injections of maintenance VIT (MVIT).

Condensation of beta-diester titanium enolates with carbonyl substrates: a combined DFT and experimental investigation.

The condensation of dialkyl beta-diesters with various aldehydes promoted by TiCl4 has been studied by DFT approaches and experimental methods, including NMR, IR and UV/Vis spectroscopy. Various possible reaction pathways have been investigated and their energy profiles evaluated to find out a plausible mechanism of the reaction. Theoretical results and experimental evidence point to a three-step mechanism: 1) Ti-induced formation of the enolate ion; 2) aldol reaction between the enolate ion and the aldehyde, both coordinated to titanium; and 3) intramolecular elimination that leads to a titanyl complex.

TiCl4/Et3N-promoted three-component condensation between aromatic heterocycles, aldehydes, and active methylene compounds.

A one-pot methodology for the synthesis of polyfunctionalized indole derivatives by a TiCl4/Et3N-promoted trimolecular condensation of aldehydes, indole heterocycles, and various activated carbonyl compounds is reported. Rationalization of these reactions and extension to other heterocyclic systems is also described.

Prevalence and risk factors for latex-related diseases among healthcare workers in an Italian general hospital.

Latex allergy has become an occupational hazard among healthcare workers. Atopy and degree of exposure have been recognized as predisposing factors for latex sensitization. We investigated the prevalence of latex allergy and the potential risk factors for latex sensitization, by distributing a questionnaire to 284 employees of a general hospital in central Italy.

Successful bridging from a peptide to a non peptide antagonist at the human tachykinin NK-2 receptor.

Non peptide products have been found to show nanomolar binding and functional affinities at the human tachykinin NK-2 receptor. The new antagonists do not possess stereogenic centers and their thermal behaviour in solution is featured by a peculiar set of conformational stereoisomers. A macroscopic viewpoint is preferentially adopted to rationalize the obtained results.

Insertion of 2-carboxysuccinate and tricarballylic acid fragments into cyclic-pseudopeptides: new antagonists for the human tachykinin NK-2 receptor.

A series of cyclic pseudopeptides were synthesized containing the sequence -Trp-Phe-(D)-PhePsiCH2NH-, the terminal ends of which were bound to 2-carboxy succinate or enantiomerically enriched tricarballylic acid to give the final cyclic structures. These two molecules and their subsequent derivatives were screened for h-NK2 receptor binding and functional antagonist activity on the rabbit urinary bladder.

Eventual error caused by dehydration with pachometry.

Among the possible variables responsible for systemic errors in the acquisition of pachometric measurements, the corneal hydration condition plays a determinant role. In the present study, the authors have investigated the importance of this condition with two different pachometers (Storz Corneoscan II and Allergan Humphrey), reproducing an experimental dehydrated condition. The main datum arising from the comparison of the measurements obtained is represented by the different time course of the value of the measurement in the two groups.

Regio- and stereoselective cycloadditions of cyclic nitrones to maleic diamide forced in a peptide: synthesis of potent ligands of human NK-2 receptor.

The regioselectivity and the stereoselectivity induced by relatively small peptidomimetic maleic diamide 1 in cycloaddition reactions with cyclic nitrones 2-5 was studied. The high regio- and stereoselectivity observed, sensibly increased by nonpolar solvents, was the effect of a double-asymmetric induction produced by the nitrone substituent on the pseudopeptidic tether. A new class of potent human tachykinin NK-2 receptor ligands was synthesized.

Molecular determinants of peptide and nonpeptide NK-2 receptor antagonists binding sites of the human tachykinin NK-2 receptor by site-directed mutagenesis.

A series of 14 mutants on nine selected residues of the human tachykinin NK(2) receptor was produced and stably transfected into CHO cells to investigate the binding of the peptide MEN 11420 and the nonpeptide SR 48968 antagonists. The main interactions found for MEN 11420 were with Thr171, Tyr206, Tyr266 and Phe270. In the case of SR 48968 crucial residues were Tyr266 and Tyr289.

Antimuscarinic, calcium channel blocker and tachykinin NK2 receptor antagonist actions of otilonium bromide in the circular muscle of guinea-pig colon.

We have analyzed, by the sucrose gap method, the action of otilonium bromide, a quaternary ammonium derivative in use for the symptomatic therapy of irritable bowel syndrome, on the electrical and mechanical responses initiated by different stimuli in the circular muscle of the guinea-pig proximal colon. Otilonium bromide produced a concentration-dependent inhibition of membrane depolarization (IC50 4.1 microM), action potentials (APs) and contraction (IC50 3.