Beyond lectures and practical courses: Teaching pharmacology using imaginative pedagogical tools.

Pharmacology has broadened its scope considerably in recent decades. Initially, it was of interest to chemists, doctors and pharmacists. In recent years, however, it has been incorporated into the teaching of biologists, molecular biologists, biotechnologists, chemical engineers and many health professionals, among others. Traditional teaching methods, such as lectures or laboratory work, have been superseded by the use of new pedagogical approaches to enable a better conceptualization and understanding of the discipline. In this article, we present several new methods that have been used in Spanish universities. Firstly, we describe a teaching network that has allowed the sharing of pedagogical innovations in Spanish universities. A European experience to improve prescribing safety is described in detail. The use of popular films and medical TV series in biomedical students shows how these audiovisual resources can be helpful in teaching pharmacology. The use of virtual worlds is detailed to introduce this new approach to teaching. The increasingly important area of the social aspects of pharmacology is also considered in two sections, one devoted to social pharmacology and the other to the use of learning based on social services to improve understanding of this important area. Finally, the use of Objective Structured Clinical Evaluation in pharmacology allows to know how this approach can help to better evaluate clinical pharmacology students. In conclusion, this article allows to know new pedagogical methods resources used in some Spanish universities that may help to improve the teaching of pharmacology.

Numerical simulation of knotted solutions for Maxwell equations.

In this work, we use the finite differences in time domain (FDTD) numerical method to compute and assess the validity of Hopf solutions, or hopfions, for the electromagnetic field equations. In these solutions, field lines form closed loops characterized by different knot topologies which are preserved during their time evolution. Hopfions have been studied extensively in the past from an analytical perspective but never, to the best of our knowledge, from a numerical approach. The implementation and validation of this technique eases the study of more complex cases of this phenomena; e.g., how these fields could interact with materials (e.g., anisotropic or nonlinear), their coupling with other physical systems (e.g., plasmas), and also opens the path on their artificial generation by different means (e.g., antenna arrays or lasers).

Genetic polymorphisms of CYP2C9 and CYP2C19 are not related to drug-induced idiosyncratic liver injury (DILI).

BACKGROUND AND PURPOSE: The general view on the pathogenesis of drug-induced idiosyncratic liver injury (DILI) is that parent compounds are rendered hepatotoxic by metabolism, mainly by cytochrome (CYP) 450, although other metabolic pathways can contribute. Anecdotal reports suggest a role of CYP 450 polymorphisms in DILI. We aimed to assess in a series of Spanish DILI patients the prevalence of important allelic variants of CYP2C9 and CYP2C19, known to be involved in the metabolism of several hepatotoxic drugs. EXPERIMENTAL APPROACH: Genotyping of CYP2C9 ((*)2, (*)3) and CYP2C19 ((*)2 and (*)3), was carried out in a total of 28 and 32 patients with a well established diagnosis of DILI. CYP2C9 and CYP2C19 variants were analysed in genomic DNA by means of PCR-FRET and compared with previous findings in other Caucasian populations. KEY RESULTS: CYP2C9 and CYP2C19 allele and genotype frequencies were in agreement with Hardy-Weinberg equilibrium. Fourteen patients (50%) were heterozygous and 1(4%) found to be compound heterozygous for the CYP2C9 allele. Seven (22%) were found to carry one and 1(3%) carried two CYP2C19 mutated alleles. No patients were homozygous for (*)3 allele. The distribution of both CYP2C9 and CYP2C19 allelic variants in DILI patients were similar to those in other Caucasian populations. Patients with variant and those with wild-type alleles did not differ in regard to clinical presentation of DILI, type of injury and outcome. CONCLUSIONS AND IMPLICATIONS: We find no evidence to support CYP2C9 and CYP2C19 genetic polymorphisms as predictable potential risk factors for DILI.

Variations in blood levels of aminoglycosides related to in vitro anticoagulant usage.

Aminoglycosides (AMG) remain an important therapeutic modality for the treatment of gram-negative infections. Adequate AMG levels have been associated with a lower risk of toxicity. Because AMG levels cannot be predicted with confidence, drug concentrations need to be measured. The authors studied the effect of different anticoagulants on AMG concentrations, which were determined by enzyme immunoanalysis. Blood samples from patients treated with AMG were obtained, and were immediately distributed in five tubes containing EDTA, sodium-citrate, or heparin at concentrations of 5 and 50 U/ml; one serum aliquot was kept as a control. All AMG determinations were performed by the enzyme multiplied immunoassay technique with Cobas-Mira equipment. The average coefficient of variations was < 3%. All samples were run the same day. Analysis of variance for repeated measures was used. Twenty-four patients (21 male and 6 female) with a mean age of 50 years (95% confidence interval = 43 to 58) and mean serum creatinine concentrations of 0.87 to 0.29 +/- Standard Deviation received 89% gentamicin and 11% tobramycin. Peak levels of AMG obtained from plasma collected with sodium citrate or heparin were significantly lower (p < 0.001) than in serum or plasma collected with EDTA. The higher the level of AMG in serum, the greater the discrepancies between drug concentrations measured with different anticoagulants. The anticoagulant used was of critical importance in determining AMG blood levels, which were underestimated when citrate or heparin were present.

Aminoglycoside-associated nephrotoxicity in extrahepatic obstructive jaundice.

Experimental data demonstrate that biliary obstruction increases renal sensitivity to gentamicin. In the present study the incidence of and risk factors for aminoglycoside nephrotoxicity were prospectively studied in patients with extrahepatic obstructive jaundice. Two hundred and thirty-seven hospitalized adult patients were classified into three groups. Group I consisted of 84 patients with extrahepatic obstructive jaundice, who received aminoglycoside (gentamicin or tobramycin). Group II consisted of 81 patients with extrahepatic obstructive jaundice, who received either antibiotics other than aminoglycoside or no antimicrobial therapy. Group III consisted of 72 noncholestatic patients receiving aminoglycosides for different disorders. Nephrotoxicity developed in 27 patients (32%) in group I vs 9 patients (11%) in group II and 4 patients (5.6%) in group III (p < 0.00001). In group I, a comparison of patients with and without nephrotoxicity revealed significantly higher values in the former for mean serum bilirubin concentration, initial steady-state trough aminoglycoside concentration and estimated half-life. Stepwise multivariate analysis with nephrotoxicity status as the dependent variable determined that the most significant variable for predicting nephrotoxicity was serum total bilirubin level. In extrahepatic cholestasis a high serum bilirubin level is a distinct factor predisposing to aminoglycoside nephrotoxicity.