Learning: New Strategy for Humanized Digital Medical Education and Training in Cardiology.

Background: The consolidation of new educational paradigms requires the implementation of innovative strategies to transform students into competent professionals.

Objectives: To assess knowledge and satisfaction of medical students before and after the use of a new humanized digital model of active learning, called virtual case-based learning (VCBL).

Methods: This was a descriptive, documentary analysis of the teaching-learning process of medical students.

Effect of preheating on the maintenance of body temperature in surgical patients: a randomized clinical trial.

Objective: to evaluate the effect of preheating on the maintenance of body temperature of patients submitted to elective gynecological surgeries.

Method: eighty-six patients were randomized, without blinding, to receive usual care (heating with a cotton sheet and blanket) or preheating with a forced air system for 20 minutes (38°C). All patients were actively heated during the intraoperative period.

Final Demonstration of the Co-Identity of Lipiarmycin A3 and Tiacumicin B (Fidaxomicin) through Single Crystal X-ray Analysis.

Lipiarmycin A3 and tiacumicin B possess the same chemical structure and have been considered identical till recently, when some authors have suggested the possibility of a minor difference between the chemical structures of the two antibiotics. In this work we performed a comparative X-ray analysis of lipiarmycin A3 and tiacumicin B. Although the commercial samples of the aforementioned compounds crystallize into two different crystal systems-evidently due to the different crystallization conditions-their chemical structures are identical.

The Co-identity of Lipiarmycin A3 and Tiacumicin B.

The co-identity of the antibiotics lipiarmycin A3 obtained from Actinoplanes deccanensis and tiacumicin B obtained from Dactylosporangium aurantiacum was unambiguously demonstrated through a number of experimental means. Spectroscopic analyses performed on both the antibiotics themselves and on their derivatives showed no difference between the two series of compounds. Moreover, unambiguous confirmation of the postulated identity of the two compounds was achieved by chemical degradation of lipiarmycin A3 and isolation of (3S,4R)-pentane-1,3,4-triol triacetate whose relative configuration was assigned by comparison with the authentic erythro and threo pentane-1,3,4-triol triacetates, obtained by chemical synthesis.

Investigation of the stereochemical course of ene reductase-catalysed reactions by deuterium labelling.

The stereoselective reduction of suitably substituted C═C bonds mediated by enzymes, called ene reductases, has received great attention in the last decade. Some successful applications of this biocatalysed procedure to the synthesis of chiral active pharmaceutical ingredients have been reported in the literature. The generation of suitable models to be used for predicting the stereochemical outcome of this kind of reductions is a challenging task.

The co-identity of lipiarmycin A3 and tiacumicin B.

The co-identity of the antibiotics lipiarmycin A3 obtained from Actinoplanes deccanensis and tiacumicin B obtained from Dactylosporangium aurantiacum was unambiguously demonstrated through a number of experimental means. Spectroscopic analyses performed on both the antibiotics themselves and on their derivatives showed no difference between the two series of compounds. Moreover, unambiguous confirmation of the postulated identity of the two compounds was achieved by chemical degradation of lipiarmycin A3 and isolation of (3S,4R)-pentane-1,3,4-triol triacetate whose relative configuration was assigned by comparison with the authentic erythro and threo pentane-1,3,4-triol triacetates, obtained by chemical synthesis.

Intermittent simulated moving bed chromatographic separation of (RS,RS)-2-(2,4-difluorophenyl)butane-1,2,3-triol.

The pharmaceutically relevant compound (RS,RS)-2-(2,4-difluorophenyl)butane-1,2,3-triol, an important intermediate in the production of different antifungal drugs, is synthesized in racemic form. For further use in the laboratory the compound has to be separated into its pure enantiomers. This work describes the different steps required to set up a chiral separation using intermittent simulated moving bed chromatography (I-SMB).

Validating a strategy for molecular dynamics simulations of cyclodextrin inclusion complexes through single-crystal X-ray and NMR experimental data: a case study.

A theoretical and experimental study about the formation and structure of the inclusion complex (-)-menthyl-O-beta-D-glucopyranoside 1 with beta-cyclodextrin (beta-CD) 2 is presented as paradigmatic case study to test the results of molecular dynamics (MD) simulations. The customary methodological approach-the use of experimental geometrical parameters as restraints for MD runs-is logically reversed and the calculated structures are a posteriori compared with those obtained from NMR spectroscopy in D(2)O solution and single crystal X-ray diffraction so as to validate the simulation procedure. The guest molecule 1 allows for a broad repertoire of intermolecular interactions (dipolar, hydrophobic, hydrogen bonds) concurring to stabilize the host-guest complex, thus providing the general applicability of the simulation procedure to cyclodextrin physical chemistry.

Applications of biocatalysis in fragrance chemistry: the enantiomers of alpha-, beta-, and gamma-irones.

The history of iris extracts, and of the isolation and enzyme-mediated synthesis of their odoriferous principle, the "irones", will be used to describe the improvement brought about by chemistry and biocatalysis in the development of natural fragrances. In particular, this tutorial review will discuss how the progress in the field of enzyme chemistry allowed the optimisation of accelerated procedures for the preparation of natural irone extracts, and the synthesis of all the ten isomers of irone, starting from commercial irone alpha.

Monitoring the synthetic procedures of commercial drugs by 2H NMR spectroscopy: the case of ibuprofen and naproxen.

We determined the D/H isotope ratios of some ibuprofen and naproxen samples by (2)H NMR spectroscopy. Some of these values were found to be useful for collecting hints on the synthetic procedures employed to prepare these drugs. Site-specific isotope ratio analysis shows great potentials in the fight against patent infringement.

Impurities of tazarotene: isolation and structural characterisation.

Two impurities showing structures 5 and 6 were isolated and characterised by means of NMR analysis, during the optimisation of a synthetic procedure to tazarotene. Impurity 5, i.e.

Traceability of synthetic drugs by position-specific deuterium isotope ratio analysis: the case of Prozac and the fluoxetine generics.

Samples of fluoxetine of different origin were submitted to natural abundance 2H NMR spectroscopy. The deuterium content at the various sites of the molecule was found to depend on its synthetic history. Hints on the synthetic procedure can be obtained by comparison with standard compounds, whose synthesis is known.

Recent advances in the benzannulation of substituted 3-alkoxycarbonyl-3,5-hexadienoic acids and 3-alkoxycarbonylhex-3-en-5-ynoic acids to polysubstituted aromatics.

The benzannulation reactions of substituted 3-alkoxycarbonyl-3,5-hexadienoic and 3-alkoxycarbonylhex-3-en-5-ynoic acids offer a straightforward access to various polysubstituted aromatic compounds. The process is very flexible, and can be applied to the regiospecific preparation of oligoaryls, naphthalenes, ring-fused heterocycles, chiral tetrahydronaphthalenes, C-aryl-glycosides and many natural products of different structure. In this Concept article, we highlight the potential of this annulation reaction by illustration of our recent contribution to this field, as well as the studies previous reported by others.

Enzyme-mediated preparation of the enantiomerically enriched isomers of the odorous tetrahydropyranyl acetates Jasmal and Jessemal, and their olfactory evaluation.

All four stereoisomers of the fragrance Jasmal of structure 3,4,5,6-tetrahydro-3-pentyl-2H-pyran-4-yl acetate were prepared by enzymatic resolutions of the corresponding alcohols. The absolute configurations were unambiguously determined by comparison with the enantiomer (3R,4S)-1 prepared from L-tartaric acid. The four stereoisomers of the fragrance Jessemal of structure 3-butyl-5-methyl-3,4,5,6-tetrahydro-2H-pyran-4-yl acetate were obtained starting from the epoxy alcohol 10, which was obtained in an optically pure state by enzymatic resolution of the racemic mixture.

Odor and (bio)diversity: single enantiomers of chiral fragrant substances.

Our sense of smell is enantioselective. This review reports interesting examples of single stereoisomers of natural and synthetic odorants, prepared via bioorganic routes, that support this statement. This article is the summary of a talk given at the Flavours & Fragrances 2004 conference in Manchester at the MCC/UMIST, 12-14 May, 2004.

Isolation and characterisation of a phenolic impurity in a commercial sample of duloxetine.

A phenolic impurity of duloxetine hydrochloride was isolated and characterised (MS, NMR, X-ray-analysis).

Isolation and characterisation of impurities in adapalene.

Three impurities of structure 2-4 were isolated and characterised during the optimisation of a synthetic procedure to adapalene. Impurity 1 was a by-product of the Friedel-Crafts reaction of adamantanol with 4-bromoanisole. Impurities 3 and 4 were due to side reactions of the final Negishi coupling.

Evaluation of asymptomatic patients with chronic Chagas disease through ambulatory electrocardiogram, echocardiogram and B-Type natriuretic peptide analyses.

Objective: To evaluate asymptomatic patients with chronic Chagas disease to determine prevalence of ventricular arrhythmias, left ventricular dysfunction, and B-type natriuretic peptide (BNP) plasma levels.

Methods: One hundred and six patients from the Chagas disease outpatient clinic underwent clinical evaluation, electrocardiogram (ECG), cardiothoracic index (CTI), ambulatory electrocardiogram (Holter monitoring), echocardiogram, and BNP measurement and then were distributed into three groups: GI, with normal ECG (n = 50); GIIA, with ECG changes characteristic of Chagas disease (n = 31); and GIIB, with other ECG changes (n = 25).

Results: The most common electrocardiographic changes were the following.

Enzymatic approach to enantiomerically pure 5-alken-2,4-diols and 4-hydroxy-5-alken-2-ones: application to the synthesis of chiral synthons.

Enantiomerically pure 1,3-diols 1-3 were obtained by a chemoenzymatic approach (lipase PS from Burkholderia cepacia). These diols were converted into useful chiral synthons, which could be considered homologues of glyceraldehyde and glyceric acid acetonides. Applications of these synthons to the de novo synthesis of sugars and preparation of conagenin carboxylic moiety were shown.

The prediction of isotopic patterns in phenylpropanoids from their precursors and the mechanism of the NIH-shift: basis of the isotopic characteristics of natural aromatic compounds.

The theoretical 2H-distribution in the aromatic ring of phenylpropanoids can be predicted from that of their precursors--erythrose-4-phosphate, phosphoenolpyruvate and NADPH--and by invoking the mechanism of the NIH-shift and implied deuterium isotope effects. For each position in the non-oxygenated ring, the predicted natural 2H-abundance is in excellent agreement with experimental data obtained from quantitative 2H NMR-measurements on natural compounds, especially concerning the relative 2H-abundances p > o > or = m. For the p-hydroxylated derivatives, the experimentally determined 2H-abundance sequence order m > o can also be deduced, assuming an anisotropic migration (intramolecular isotope effect) of the p-hydrogen atom to the two differently 2H-substituted m-positions during the NIH-shift (intramolecular hydrogen transfer) and an in vivo deuterium kinetic isotope effect of approximately 1.

Determination of the synthetic origin of methamphetamine samples by 2H NMR spectroscopy.

Samples of methamphetamine, prepared according to the most common synthetic pathways, were submitted to natural-abundance 2H NMR spectroscopy. The deuterium content at the various sites of the molecule was found to depend on its synthetic history. The technique provides a chemical fingerprint of methamphetamine samples and can give hints to trace back the starting materials and the synthetic procedures.

Stable isotope characterization of the ortho-oxygenated phenylpropanoids: coumarin and melilotol.

The natural abundance 2H NMR spectra of extractive coumarin 10 and of its dihydroderivative melilotol 11 produced by baker's yeast reduction has been compared with synthetic materials. Diagnostic for the differentiation of 10 are the (D/H)beta values, which are in the 128.1-133.

Impurity analysis of retinoic acid samples.

The structure of an impurity contained in samples of all trans-retinoic acid was established by means of NMR and MS spectra, and confirmed by X-ray diffraction analysis. The chemical structure of the impurity 2 was found to be strictly correlated to the synthetic procedure employed for the preparation of the retinoic acid samples. Single crystal analysis allowed us to characterise the molecular conformation and the crystal structure of 2.

Biocatalytic preparation of natural flavours and fragrances.

During the past years biocatalytic production of fine chemicals has been expanding rapidly. Flavours and fragrances belong to many different structural classes and therefore represent a challenging target for academic and industrial research. Here, we present a condensed overview of the potential offered by biocatalysis for the synthesis of natural and natural-identical odorants, highlighting relevant biotransformations using microorganisms and isolated enzymes.