Bladder cancer biomarkers and their role in surveillance and screening

Early detection of bladder cancer and its recurrences is essential for improved prognosis and long-term survival. The detection and follow-up of these patients is currently based on cystoscopy, which is expensive and invasive, and, in most cases, cytology, which is non-invasive but not very sensitive. During recent years, many urine-based tests have been developed and tested in different patient populations. In this review we discuss new developments for biomarkers in bladder cancer that have potential use in surveillance and screening. In almost all publications authors compare sensitivity of the test with a concomitantly executed cystoscopy, for example, determine cross-sectional sensitivity. However, it has also been shown that false positive test results may be followed by a positive cystoscopy in the near future, showing that cystoscopy itself does not provide 100% sensitivity. This suggests that for a proper evaluation of urine-based tests, longitudinal studies should be carried out and the results communicated to the urologist.     

Psychogenic nonepileptic seizures and health-related quality of life: the relationship with psychological distress and other physical symptoms

This study explores the relationship between the frequency of psychogenic nonepileptic seizures (PNES) and health-related quality of life (HRQoL), as well as the effect of psychological distress and other physical symptoms on this relationship. Data were collected on 96 patients with PNES. Correlations of seizure frequency with HRQoL, psychological distress, and physical symptoms were computed. Partial correlations of seizure frequency with HRQoL while controlling for psychological distress and physical symptoms were also computed. Seizure frequency was found to be significantly related to subjective HRQoL, although the relationship with HRQoL was rendered nonsignificant when the effects of psychological distress and the number of other physical symptoms were taken into account. The results of this study suggest that summary scores of HRQoL are not independently related to frequency of PNES and that there is a close association between PNES frequency, levels of psychological distress, and number of other physical symptoms experienced.     

Mediators and receptors in the resolution of inflammation: drug targeting opportunities

The active resolution of inflammation is recognized as offering new opportunities to generate novel anti-inflammatory agents. The emerging appreciation of the importance of active resolution in regulation of inflammation also creates an imperative to examine developing and existing agents for their potential to influence these pathways. This themed issue of the British Journal of Pharmacology contains papers that discuss the roles of annexin-1, lipoxins and related lipid products of fish oils as well as other mechanisms involved in active resolution and their receptor targets.This article is part of a themed issue on Mediators and Receptors in the Resolution of Inflammation. To view this issue visit http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009     

Histamine H1 receptor knockout mice exhibit impaired spatial memory in the eight-arm radial maze

Background and purpose:

In the mammalian brain, histaminergic neurotransmission is mediated by the postsynaptic histamine H₁ and H₂ receptors and the presynaptic H₃ autoreceptor, which also acts as a heteroreceptor. The H₁ receptor has been implicated in spatial learning and memory formation. However, pharmacological and lesion studies have revealed conflicting results. To examine the involvement of histamine H₁ receptor in spatial reference and working memory formation, H₁ receptor knockout mice (KO) were tested in the eight-arm radial maze. Previously, we found that the H₁ receptor-KO mice showed reduced emotionality when confronted with spatial novelty. As it is known that emotions can have an impact on spatial learning and memory performance, we also evaluated H₁ receptor-KO mice in terms of emotional behaviour in the light–dark box.

Experimental approach:

Mice lacking the H₁ receptor and wild-type mice (WT) were tested for spatial reference and working memory in an eight-arm radial maze with three arms baited and one trial per day. Emotional behaviour was measured using the light–dark test.

Key results:

The H₁ receptor-KO mice showed impaired spatial reference and working memory in the radial maze task. No significant differences between H₁ receptor-KO and WT mice were observed in the light–dark test.

Conclusions and implications:

The spatial memory deficits of the H₁ receptor-KO mice might be due to the reported changes in cholinergic neurochemical parameters in the frontal cortex and the CA1 subregion of the hippocampus, to impaired synaptic plasticity in the hippocampus, and/or to a dysfunctional brain reward/reinforcement system.     

Anti-beta1-adrenergic receptor autoantibodies are potent stimulators of the ERK1/2 pathway in cardiac cells

OBJECTIVE: Antibodies specific for the beta1-adrenergic receptor (beta1AR) are highly prevalent in patients with idiopathic dilated cardiomyopathy (DCM) and known to contribute to the pathogenesis of heart failure, though the precise molecular mechanisms involved are largely unknown. METHODS: We have explored the effects of beta(1)AR autoantibodies obtained from DCM patients on extracellular signal-regulated kinase (ERK) activation in murine cardiomyocytes. RESULTS: We find that human beta(1)AR autoantibodies potently stimulate ERK1/2 in cardiac cells by using signalling pathways different from those triggered by the classic beta-agonist isoproterenol, also leading to a different pattern of activated ERK subcellular localization. The extent of ERK stimulation by endogenous cardiac beta(1)AR is markedly enhanced in the presence of both beta(1)AR-autoantibodies and isoproterenol. Interestingly, beta(1)AR-autoantibody-mediated ERK activation is not blocked by some betaAR antagonists used in the treatment of heart failure. CONCLUSIONS: Our results suggest that these antibodies elicit a distinct beta(1)AR active conformation that would lead to the engagement of signaling effectors different from those recruited by classic beta-agonists, a finding that could lead to better understanding of DCM pathogenesis and aid in designing diagnostic and therapeutic strategies.