Therapeutic inhibition of the renin angiotensin aldosterone system.

BACKGROUND: Inhibitors of the renin angiotensin aldosterone system (RAAS) represent some of the most widely prescribed, successful and well-tolerated therapeutics of recent times and are of proven worth in the management/prevention of cardiovascular disease and diabetic nephropathy. However, as knowledge has grown about the RAAS and its manifold alternate pathways, loci of action and dynamic response to inhibition, so has the clinical debate as how to best use existing therapeutics as well as how best to conceptualise and design RAAS inhibitors of the future. OBJECTIVE: To provide an overview of the several points of therapeutic anti-RAAS intervention, many of which have already been exploited from 'upstream' renin inhibition to 'midstream' ACE inhibition to 'downstream' angiotensin AT1 receptor blockade. METHODS: A search of patents for RAAS inhibitors recorded in 2008 was conducted along with a relevant literature search. RESULTS/CONCLUSION: Each intervention has merits and demerits with implications for RAAS 'escape' phenomena, 'dual inhibition' therapy, long-term clinical efficacy and adverse drug reactions. Renin inhibitors offer the most complete RAAS inhibition, but more downstream interventions are likely to recruit supplementary anti-RAAS mediators and receptor signalling pathways. Furthermore, managing hyperkalaemia-stimulated aldosterone escape during combined ACE inhibitor and angiotensin receptor blocker treatment may realise the full clinical potential of dual inhibition therapy.

Azo compounds in colon-specific drug delivery.

Azo compounds have the potential to act as drug carriers that facilitate the selective release of therapeutic agents to the colon, and also to effect the oral administration of those macromolecular drugs that require colon-specific drug delivery. With some further research-driven refinements, these materials may lead to more efficient treatments for local conditions, such as colonic cancer or inflammatory bowel disease. This article provides an overview of the azo-based systems developed to date, identifies the requirements for an ideal carrier, and highlights the directions for further developments in the field of azo group-facilitated colonic delivery.

Orally administered, colon-specific mucoadhesive azopolymer particles for the treatment of inflammatory bowel disease: An in vivo study.

Radiolabeled congeners of a series of azopolymers have been synthesized and characterized. The in vivo (rat) gastrointestinal transit profile of millimeter-sized particles of these azopolymers has been determined and used to facilitate the selection of a candidate material for therapeutic applications. The efficacy of the selected material as a protective coating for the colonic mucosa has been tested in a hapten-reactivated, in vivo model of inflammatory bowel disease: 7 days after reactivation of the condition, the myeloperoxidase activity of animals that had received doses of the selected azopolymer was determined to be at the same level as that of healthy animals or that of the negative control group, highlighting the therapeutic promise of this material.

Attitudes to concept maps as a teaching/learning activity in undergraduate health professional education: influence of preferred approach to learning.

Pre-prepared concept maps that organise knowledge in a non-linear fashion appeal to a variety of cognitive learning styles and may thus represent an educational tool that supports 'teaching to all types'. However, another central cognitive factor, learning approach, may have a bearing on student take-up of this learning resource. Student attitudes to pre-prepared concept maps introduced in Stage 2 MPharm and BSc Pharmacology lectures were therefore examined in relation to the principal learning orientations according to Duff's 30-item revised approaches to study inventory (RASI). Approximately one half of students (49.6 +/- 4.5%) reported pre-prepared concept maps to be useful to their learning (n = 121). When preferred learning approach was examined, derived from the highest RASI score per individual and excluding ties, 31.9 +/- 4.3%, 29.3 +/- 4.2% and 38.8 +/- 4.5% of students demonstrated a preference for the deep approach (DA), strategic approach (STA) and surface approach (SUA), respectively (P > 0.05, chi2 goodness-of-fit test, n = 116). There was a weak but statistically significant association between preferred learning approach identified by Duff's 30-item RASI and the self-reported usefulness of concept maps (P < 0.05, chi2 test of independence; Cramer's V = 0.235; lambda = 0.193). In contrast, gender was not significantly associated with attitude to concept maps in this student cohort. A preliminary analysis of standardised residuals based on observed and expected frequencies revealed that the greatest contributions to this significant association were: a positive influence of DA and a negative influence of STA, respectively, on attitude to concept maps. These data now indicate a contribution of the principal learning orientations vis-à-vis student attitudes to pre-prepared concept maps when employed alongside more traditional teaching/learning activities in medical and biomedical science education, and may further suggest a role for concept maps in the support of deep learning.

Attitudes to concept maps as a teaching/learning activity in undergraduate health professional education: influence of preferred learning style.

Concept maps that integrate and relate concepts in a nonlinear fashion are widely accepted as an educational tool that can underpin meaningful learning in medical education. However, student take-up may be affected by a number of cognitive and non-cognitive influences. In the present study, student attitudes to pre-prepared concept maps introduced in Stage 2 conjoint MPharm and BSc Pharmacology lectures were examined in relation to preferred learning styles according to the Felder-Silverman model. There was no statistically significant influence of dichotomous learning style dimension (sensing/intuitive; visual/verbal; active/reflector; sequential/global) on the self-reported utility of such concept maps to learning. However, when strength of preference was analysed within each dimension, moderate/strong verbal learners were found to be significantly less likely to self-report concept maps as useful relative to mild verbal learners. With this important exception, these data now suggest that student attitudes to concept maps are broadly not influenced by preferred learning styles and furthermore highlight the potential of concept maps to address a variety of different learning styles and thereby facilitate 'teaching to all types'. Concept maps could therefore potentially assist motivation, engagement and deep learning in medical and biomedical science education when used as a supplement to more traditional teaching/learning activities.

Nitrate tolerance and the links with endothelial dysfunction and oxidative stress.

Identification of nitric oxide as the molecule responsible for endothelial dependant vasodilatation has led to an explosion of interest in endothelial function. Oxidative stress has been identified as an important factor in the development of tolerance to organic nitrates. This review examines the evidence supporting this recently developed theory and how mechanisms of nitrate tolerance may link with the wider picture of primary nitric oxide resistance.