Gut hormone GPCRs: structure, function, drug discovery

Crystallization and determination of the high resolution three-dimensional structure of the β2-adrenergic receptor in 2007 was followed by structure elucidation of a number of other receptors, including those for neurotensin and glucagon. These major advances foster the understanding of structure-activity relationship of these receptors and structure-based rational design of new ligands having more predictable activity. At present, structure determination of gut hormone receptors in complex with their ligands (natural, synthetic) and interacting signalling proteins, for example, G-proteins, arrestins, represents a challenge which promises to revolutionize gut hormone endocrinonology.

Incretins and bone: friend or foe?

International audience

Ketamina para el tratamiento de la hiperalgesia causada por remifentanil en cirugía: revisión sistemática de literatura

La hiperalgesia secundaria a la administración de remifentanil se ha documentado tanto en estudios animales como en estudios experimentales en humanos y ha aumentado su incidencia dado su uso cada vez más frecuente para el mantenimiento durante diferentes procedimientos anestésicos, anestesia general balanceada, anestesia total intravenosa y sedaciones. La hiperalgesia secundaria al uso de remifentanil es un proceso pro-nociceptivo relacionado pero que difiere de la tolerancia aguda, en el que los neurotransmisores excitatorios de N- metil D aspartato (NMDA) juegan un rol central. Por tanto la ketamina se ha utilizado en diferentes dosis para la prevención de dicha hiperalgesia sin que se haya establecido su efectividad para la prevención y tratamiento de esta condición. Se encontraron 8 estudios publicados en los últimos 10 años que proponen a la ketamina como una estrategia útil y efectiva el tratamiento de la hiperalgesia inducida por el uso de remifentanil. Los resultados demuestran que la ketamina es un tratamiento costo efectivo para el tratamiento de la hiperalgesia en diferentes poblaciones sometidas a diversos procedimientos quirúrgicos y anestésicos que incluyan la administración de remifentanil tanto en la inducción como en el mantenimiento anestésico sin generar efectos secundarios adicionales, así como que logra disminuir el consumo de opioides y la EVA en el posoperatorio.

Actitudes hacia la Enfermedad del Alzheimer según el género y la edad de adultos colombianos

La enfermedad de Alzheimer (EA) es la demencia más frecuente y su prevalencia continúa en aumento tanto en Colombia como en el mundo. Esta investigación tuvo como objetivo explorar si las actitudes hacia la EA varían según la edad y género de 450 personas adultas colombianas. Se realizó un estudio exploratorio de corte transversal en el que se aplicó un cuestionario autodiligenciado. Se encontró que efectivamente hay algunas diferencias según la edad y el género en el componente cognoscitivo (creencias y conocimiento) y conductual (intención conductual y conducta) de las actitudes; y diferencias según el género en el componente afectivo. Se concluye que los conocimientos sobre la EA son escasos, que la tristeza es la emoción predominante hacia la EA y que es un tema de interés en el que predomina la idea de que afecta especialmente la memoria. Se discutieron los resultados reconociendo que esta es una aproximación inicial a las actitudes hacia la EA.

Surviving Bioscience and Pharmacology – an eBook for accelerated students in Nursing

An eBook to support accelerated nursing students is being developed at QUT. The first component of this is a formative activity comprising key bioscience and pharmacology concepts and self-help quizzes. This initiative has been reviewed favourably by the students. The eBook will also cover requisite academic skills and revision bioscience material.

“Success in (Surviving) Bioscience and Pharmacology” – an eBook to improve the retention of diploma nurses transitioning to a Bachelor of Nursing course

Diploma students transitioning into the NS40 BNursing (BN) course at QUT withdraw from the bioscience and pharmacology units, and leave the university at higher rates than traditional students. The diploma students, entering in second year, have missed out on 2 units of bioscience taught to the traditional students in their first year, and miss out on a 3rd unit of bioscience taught to the traditional students in their 2nd year. Instead the diploma students receive one specialized unit in bioscience only i.e. a bridging unit. As a consequence, the diploma students may not have the depth of bioscience knowledge to be able to successfully study the bridging unit (LSB111) or the pharmacology unit (LSB384). Our plan was to write an eBook which refreshed and reinforced diploma students’ knowledge of bioscience aiming to prepare them with the concepts and terminology, and to build a level of confidence to support their transition to the BN. We have previously developed an intervention associated with reduced attrition of diploma nursing students, and this was our starting point. The study skills part of the initial intervention was addressed in the eBook, by links to the specialist services and resources available from our liaison librarian and academic skills adviser. The introductory bioscience/pharmacology information provided by the previous intervention involved material from standard textbooks. However, we considered this material too difficult for diploma students. Thus, we created simplified diagrams to go with text as part of our eBook. The outcome is an eBook, created and made available to the diploma students via the Community Website: “Surviving Bioscience and Pharmacology”. Using simplified diagrams to illustrate the concise text, definition to explain the concepts, the focus has been on encouraging self-awareness and help-seeking strategies and building students who take responsibility for their learning. All the nursing students in the second semester LSB384 Pharmacology Unit have been surveyed face-to-face to get feedback on their engagement with the eBook resource. The data has not been analysed to date. An important consideration is that the website be evaluated by the diploma students as they come into bioscience in first semester (LSB111), the student population for whom the eBook is primarily intended. To get a good response rate we need to do a face-to-face survey. However, we have not been able to do this, as the co-ordinator of the unit has changed since we started the project, and the present co-ordinator will not allow us access to these students.

The paradigm shift in realising the right to read : how ebook libraries are enabling in the university sector

Millions of people with print disabilities are denied the right to read. While some important efforts have been made to convert standard books to accessible formats and create accessible repositories, these have so far only addressed this crisis in an ad hoc way. This article argues that universally designed ebook libraries have the potential of substantially enabling persons with print disabilities. As a case study of what is possible, we analyse 12 academic ebook libraries to map their levels of accessibility. The positive results from this study indicate that universally designed ebooks are more than possible; they exist. While results are positive, however, we also found that most ebook libraries have some features that frustrate full accessibility, and some ebook libraries present critical barriers for people with disabilities. Based on these findings, we consider that some combination of private pressure and public law is both possible and necessary to advance the right-to-read cause. With access improving and recent advances in international law, now is the time to push for universal design and equality.

EBook readers in Australian public libraries - are they REAL-e worth it

Hand-held ebook readers present many challenges for Australian libraries that want to integrate this emerging technology into their library’s service. In 2001, both Toowoomba City Library and the Brisbane City Council Library Service embarked on such projects. This paper reports on the differing experience of these two public library services, outlining difficulties encountered, customer reactions to the technology, and the central issues that acquiring and circulating these readers pose for public libraries in Australia.

Pharmacology in one semester [Version 3, Semester 1, 2014]

- For use in Introductory Units/Courses to Biomedical/Science Students - For use with Allied Health Students who are taking pharmacology as a Unit/Course or a part Unit/Course

The Pharmacology of Oxycodone : Studies In Vitro, In Vivo and In Humans

The antinociceptive properties of oxycodone and its metabolites were studied in models of thermal and mechanical nociception and in the spinal nerve ligation (SNL) model of neuropathic pain in rats. Oxycodone induced potent antinociception after subcutaneous (s.c.) administration in all models of nociception used in rats compared with morphine, methadone and its enantiomers. In the SNL model of neuropathic pain in rats, oxycodone produced dose dependent antinociception after s.c. administration. The antinociceptive effects of s.c. oxycodone were antagonized by naloxone but not by nor-binaltorphimine (Nor-BNI) a selective κ-opioid receptor antagonist indicating that the antinociceptive properties of oxycodone are predominantly μ-opioid receptor-mediated. The antinociceptive activity of oxymorphone, noroxycodone, and noroxymorphone, oxidative metabolites of oxycodone, were studied to determine their role in the oxycodone-induced antinociception in the rat. Of the metabolites of oxycodone s.c. administration of oxymorphone produced potent thermal and mechanical antinociception. Noroxycodone had a poor antinociceptive effect and noroxymorphone was inactive. Oxycodone produced naloxone-reversible antinociception after intrathecal (i.t) administration with a poor potency compared with morphine and oxymorphone. This seems to be related to the low efficacy and potency of oxycodone to stimulate μ-opioid receptor activation in the spinal cord in μ-opioid receptor agonist-stimulated (GTP)γ[S] autoradiography, compared with morphine and oxymorphone. All metabolites studied were more potent than oxycodone after i.t. administration. I.t. noroxymorphone induced a significantly longer lasting antinociceptive effect compared with the other drugs studied. The role of cytochrome P450 (CYP) 2D6-mediated metabolites on the analgesic activity of oxycodone in humans was studied by blocking the CYP2D6-mediated metabolism of oxycodone with paroxetine. Paroxetine co-administration had no effect on the analgesic effect of oxycodone compared with placebo in chronic pain patients, indicating that oxycodone-induced analgesia and adverse-effects are not dependent of the CYP2D6-mediated metabolism in humans. Although oxycodone has many pharmacologically active metabolites, they seem to have an insignificant role in oxycodone-induced antinociception in humans and rats.

Breast cancer therapies in development. A review of their pharmacology and clinical potential.

Although the management of breast cancer has improved over the past few decades, it remains an important challenge for the clinician. Cytotoxic chemotherapy and hormonotherapy, when given in the adjuvant setting, have a definitive though modest impact on the outcome of early-stage breast cancer. In metastatic disease, these therapies help to provide substantial palliation of symptoms but have a limited impact on survival. The discovery of vinorelbine and the taxanes, paclitaxel and docetaxel, certainly represented the most encouraging clinical development of the 1980s in breast cancer therapy. Several other new cytotoxic agents have been recognised for their potential in the treatment of this disorder. Many of them are only in a very early phase of their clinical development and it remains to be proven that they will have a major role in daily practice in the near future.

A Pharmacology-Based Enrichment Program for Undergraduates Promotes Interest in Science.

There is a strong need to increase the number of undergraduate students who pursue careers in science to provide the "fuel" that will power a science and technology-driven U.S. economy. Prior research suggests that both evidence-based teaching methods and early undergraduate research experiences may help to increase retention rates in the sciences. In this study, we examined the effect of a program that included 1) a Summer enrichment 2-wk minicourse and 2) an authentic Fall research course, both of which were designed specifically to support students' science motivation. Undergraduates who participated in the pharmacology-based enrichment program significantly improved their knowledge of basic biology and chemistry concepts; reported high levels of science motivation; and were likely to major in a biological, chemical, or biomedical field. Additionally, program participants who decided to major in biology or chemistry were significantly more likely to choose a pharmacology concentration than those majoring in biology or chemistry who did not participate in the enrichment program. Thus, by supporting students' science motivation, we can increase the number of students who are interested in science and science careers.