British Journal of Pharmacology

Free radicals and other reactive species (RS) are thought to play an important role in many human diseases. Establishing their precise role requires the ability to measure them and the oxidative damage that they cause.

British Journal of Pharmacology(2004)142, 231–255. doi:10.1038/sj.bjp.0705776

Ba đồng phân của l‐arginine đã được xác định là những chất ức chế synthase nitric oxide (NO) nội mô bằng cách đo lường tác động của chúng lên synthase NO nội mô từ động mạch chủ lợn, trên trương lực mạch của vòng động mạch chủ chuột và trên huyết áp của chuột có gây mê.

Cannabis sativa is the source of a unique set of compounds known collectively as plant cannabinoids or phytocannabinoids. This review focuses on the manner with which three of these compounds, (−)‐trans‐Δ⁹‐tetrahydrocannabinol (Δ⁹‐THC), (−)‐cannabidiol (CBD) and (−)‐trans‐Δ⁹‐tetrahydrocannabivarin (Δ⁹‐THCV), interact with cannabinoid CB₁ and CB₂ receptors. Δ⁹‐THC, the main psychotropic constituent of cannabis, is a CB₁ and CB₂ receptor partial agonist and in line with classical pharmacology, the responses it elicits appear to be strongly influenced both by the expression level and signalling efficiency of cannabinoid receptors and by ongoing endogenous cannabinoid release. CBD displays unexpectedly high potency as an antagonist of CB₁/CB₂ receptor agonists in CB₁‐ and CB₂‐expressing cells or tissues, the manner with which it interacts with CB₂ receptors providing a possible explanation for its ability to inhibit evoked immune cell migration. Δ⁹‐THCV behaves as a potent CB₂ receptor partial agonist in vitro. In contrast, it antagonizes cannabinoid receptor agonists in CB₁‐expressing tissues. This it does with relatively high potency and in a manner that is both tissue and ligand dependent. Δ⁹‐THCV also interacts with CB₁ receptors when administered in vivo, behaving either as a CB₁ antagonist or, at higher doses, as a CB₁ receptor agonist. Brief mention is also made in this review, first of the production by Δ⁹‐THC of pharmacodynamic tolerance, second of current knowledge about the extent to which Δ⁹‐THC, CBD and Δ⁹‐THCV interact with pharmacological targets other than CB₁ or CB₂ receptors, and third of actual and potential therapeutic applications for each of these cannabinoids.

British Journal of Pharmacology (2008) 153, 199–215; doi:10.1038/sj.bjp.0707442; published online 10 September 2007

For many years, the central nervous system (CNS) was considered to be ‘immune privileged’, neither susceptible to nor contributing to inflammation. It is now appreciated that the CNS does exhibit features of inflammation, and in response to injury, infection or disease, resident CNS cells generate inflammatory mediators, including proinflammatory cytokines, prostaglandins, free radicals and complement, which in turn induce chemokines and adhesion molecules, recruit immune cells, and activate glial cells. Much of the key evidence demonstrating that inflammation and inflammatory mediators contribute to acute, chronic and psychiatric CNS disorders is summarised in this review. However, inflammatory mediators may have dual roles, with detrimental acute effects but beneficial effects in long‐term repair and recovery, leading to complications in their application as novel therapies. These may be avoided in acute diseases in which treatment administration might be relatively short‐term. Targeting interleukin (IL)‐1 is a promising novel therapy for stroke and traumatic brain injury, the naturally occurring antagonist (IL‐1ra) being well tolerated by rheumatoid arthritis patients. Chronic disorders represent a greater therapeutic challenge, a problem highlighted in Alzheimer's disease (AD); significant data suggested that anti‐inflammatory agents might reduce the probability of developing AD, or slow its progression, but prospective clinical trials of nonsteroidal anti‐inflammatory drugs or cyclooxygenase inhibitors have been disappointing. The complex interplay between inflammatory mediators, ageing, genetic background, and environmental factors may ultimately regulate the outcome of acute CNS injury and progression of chronic neurodegeneration, and be critical for development of effective therapies for CNS diseases.

British Journal of Pharmacology (2006) 147, S232–S240. doi:10.1038/sj.bjp.0706400

With more than 20 molecules in clinical use, monoclonal antibodies have finally come of age as therapeutics, generating a market value of $11 billion in 2004, expected to reach $26 billion by 2010. While delivering interesting results in the treatment of several major diseases including autoimmune, cardiovascular and infectious diseases, cancer and inflammation, clinical trials and research are generating a wealth of useful information, for instance about associations of clinical responses with Fc receptor polymorphisms and the infiltration and recruitment of effector cells into targeted tissues. Some functional limitations of therapeutic antibodies have come to light such as inadequate pharmacokinetics and tissue accessibility as well as impaired interactions with the immune system, and these deficiencies point to areas where additional research is needed. This review aims at giving an overview of the current state of the art and describes the most promising avenues that are being followed to create the next generation of antibody‐based therapeutic agents.

This article is part of a themed section on Vector Design and Drug Delivery. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009

Endothelial dysfunction plays a key role in the pathogenesis of diabetic vascular disease. The endothelium controls the tone of the underlying vascular smooth muscle through the production of vasodilator mediators. The endothelium‐derived relaxing factors (EDRF) comprise nitric oxide (NO), prostacyclin, and a still elusive endothelium‐derived hyperpolarizing factor (EDHF). Impaired endothelium‐dependent vasodilation has been demonstrated in various vascular beds of different animal models of diabetes and in humans with type 1 and 2 diabetes. Several mechanisms of endothelial dysfunction have been reported, including impaired signal transduction or substrate availibility, impaired release of EDRF, increased destruction of EDRF, enhanced release of endothelium‐derived constricting factors and decreased sensitivity of the vascular smooth muscle to EDRF. The principal mediators of hyperglycaemia‐induced endothelial dysfunction may be activation of protein kinase C, increased activity of the polyol pathway, non‐enzymatic glycation and oxidative stress. Correction of these pathways, as well as administration of ACE inhibitors and folate, has been shown to improve endothelium‐dependent vasodilation in diabetes. Since the mechanisms of endothelial dysfunction appear to differ according to the diabetic model and the vascular bed under study, it is important to select clinically relevant models for future research of endothelial dysfunction.

British Journal of Pharmacology(2000)130, 963–974; doi:10.1038/sj.bjp.0703393