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The long-standing debate that polyphenol secondary metabolites from dietary plants are important nutritional components continues due to compelling evidence for their abilities to ameliorate degenerative conditions including, cancer, neurological disorders and cardiovascular disease. The clinical use of polyphenols is not, however, mainstream as issues regarding poor selectivity, dosage, toxicity and delivery methods are unresolved. The paper by Rieder et al. suggests that the lack of selectivity, at least for the stilbene, resveratrol, may not be a major limiting factor. The present commentary is a critique of this significant finding that is focused on deciding how the use of resveratrol as clinical medicine could be advanced, and how this new information integrates with current knowledge of polyphenol physiological effects. This commentary suggests that the multi-target nature of polyphenols may be translated into reliable therapy using the current systems/network pharmacology approach concerned with developing viable therapeutic agents that achieve specific effects through interactions with a wide array of targets. Linked Article This article is a commentary on Rieder et al., pp. 1244-1258 of BJP 167:6. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2012.02063.x [ABSTRACT FROM AUTHOR]

As our knowledge and understanding of the way in which GPCRs operate continues to grow rapidly, many new opportunities are emerging to develop novel therapeutic agents. This themed issue of the British Journal of Pharmacology contains a series of papers that cover recent developments and identify approaches that may help determine future directions. Many of these papers contain material that was presented at the 6th International Molecular Pharmacology of G Protein-Coupled Receptors meeting held at the Monash Institute of Pharmaceutical Sciences in Melbourne Australia in late 2010. LINKED ARTICLES This article is part of a themed section on the Molecular Pharmacology of G Protein-Coupled Receptors (GPCRs). To view the other articles in this section visit . To view the 2010 themed section on the same topic visit [ABSTRACT FROM AUTHOR]

There is a high incidence of psychiatric comorbidity in people with epilepsy ( PWE), particularly depression. The manifold adverse consequences of comorbid depression have been more clearly mapped in recent years. Accordingly, considerable efforts have been made to improve detection and diagnosis, with the result that many PWE are treated with antidepressant drugs, medications with the potential to influence both epilepsy and depression. Exposure to older generations of antidepressants (notably tricyclic antidepressants and bupropion) can increase seizure frequency. However, a growing body of evidence suggests that newer ('second generation') antidepressants, such as selective serotonin reuptake inhibitors or serotonin-noradrenaline reuptake inhibitors, have markedly less effect on excitability and may lead to improvements in epilepsy severity. Although a great deal is known about how antidepressants affect excitability on short time scales in experimental models, little is known about the effects of chronic antidepressant exposure on the underlying processes subsumed under the term 'epileptogenesis': the progressive neurobiological processes by which the non-epileptic brain changes so that it generates spontaneous, recurrent seizures. This paper reviews the literature concerning the influences of antidepressants in PWE and in animal models. The second section describes neurobiological mechanisms implicated in both antidepressant actions and in epileptogenesis, highlighting potential substrates that may mediate any effects of antidepressants on the development and progression of epilepsy. Although much indirect evidence suggests the overall clinical effects of antidepressants on epilepsy itself are beneficial, there are reasons for caution and the need for further research, discussed in the concluding section. [ABSTRACT FROM AUTHOR]

Retinoids play important roles in the transcriptional activity of normal, degenerative and tumour cells. Retinoid analogues may be promising therapeutic agents for the treatment of immune disorders as different as type I diabetes and systemic lupus erythematosus. In addition, the use of retinoids in cancer treatment has progressed significantly in the last two decades; thus, numerous retinoid compounds have been synthesized and tested. In this paper, the actual or potential use of retinoids as immunomodulators or tumour-suppressive agents is discussed. [ABSTRACT FROM AUTHOR]

The limitations of traditional anticoagulants, heparin and warfarin, have prompted the development of new anticoagulant drugs for prevention and treatment of both venous and arterial thromboembolism. After a brief review of thrombogenesis and its regulation, this paper focuses on new anticoagulant agents in more advanced stages of clinical testing.British Journal of Pharmacology (2005) 144, 1017-1028. doi:10.1038/sj.bjp.0706153 [ABSTRACT FROM AUTHOR]

Metastatic bone disease is a serious clinical complication for the treatment of patients with advanced cancer, but few therapeutic options are currently available. Bisphosphonates are an established standard care for these patients, but new treatments are now emerging, including the use of monoclonal antibodies targeting the RANK ligand. In this issue of the BJP, Reuter et al. provide evidence that thiocolchicoside, a semi-synthetic derivative of the naturally occurring colchicoside, extracted from the seeds of Gloriosa superba (Liliaceae), prevented osteoclactogenesis by suppressing RANK ligand-mediated NF-κB activation. Thiolcolchicoside may thus represent an attractive therapeutic option for the management of bone metastatic disease. LINKED ARTICLE This article is a commentary on Reuter et al., pp. 2127-2139 of this issue. To view this paper visit [ABSTRACT FROM AUTHOR]

This article summarizes the findings of Kameda et al. (this issue of BJP) that suggest a new avenue for the pharmacological treatment of subarachnoid haemorrhage (SAH) involving the combined use of a proteinase inhibitor (argatroban) that targets thrombin and an antioxidant (vitamin C). The findings are presented in the context of previous modalities of treating SAH that are of modest impact and the possibility that inhibiting proteinase-mediated signalling via proteinase-activated receptors like the thrombin PAR1 receptor combined with blocking oxidative stress may provide a new avenue for the treatment of SAH. LINKED ARTICLE This article is a commentary on Kameda et al., pp. 106-119 of this issue. To view this paper visit [ABSTRACT FROM AUTHOR]

A conference paper about the effect of the withdrawal of endogenous estrogen by ovariectomy and the replacement by chronic administration of 17β-estradiol on ischemia-induced arrhythmias is presented. It discusses that female Wistar rats are ovariectomized under Hypnorm/diazepam anesthesia. Results show that chronic administration of 17β-estradiol does not significantly reduce ischemia-induced arrhythmias.