Histamine-induced itch and its relationship with pain

Itch is one of the major complications of skin diseases. Although there are various substances that induce itch or pruritus, it is evident that histamine is the best known endogenous agent that evokes itch. Even though histamine-induced itch has been studied for some time, the underlying mechanism of itch is just beginning to emerge. Although various downstream signaling pathways of histamine receptors have been revealed, more studies are required to determine the cause of histamine-induced itch. It appears that itch and pain involve different neuronal pathways. Pain generally inhibits itch, which indicates an inter-communication between the two. Complex interactions between itch and pain may be expected based on reports on disease states and opioids. In this review, we discuss the molecular mechanism and the pharmacological aspects of histamine-induced itch. Especially, the underlying mechanism of TRPV1 (an anti-pruritus target) has been determined to some extent

ProsCan for Couples: Randomised controlled trial of a couples-based sexuality intervention for men with localised prostate cancer who receive radical prostatectomy

Background: Prostate cancer is the most common male cancer in the Western world. The most substantial long term morbidity from this cancer is sexual dysfunction with consequent adverse changes in couple and intimate relationships. Research to date has not identified an effective way to improve sexual and psychosocial adjustment for both men with prostate cancer and their partners. As well, the efficacy and cost effectiveness of peer counselling as opposed to professional models of service delivery has not yet been empirically tested. This paper presents the design of a three arm randomised controlled trial (peer vs. nurse counselling vs. usual care) that will evaluate the efficacy of two couples-based sexuality interventions (ProsCan for Couples: Peer support vs. nurse counselling) on men's and women's sexual and psychosocial adjustment after surgical treatment for localised prostate cancer; in addition to cost-effectiveness. Methods/design: Seventy couples per condition (210 couples in total) will be recruited after diagnosis and before treatment through urology private practices and hospital outpatient clinics and randomised to (1) usual care; (2) eight sessions of peer-delivered telephone support with DVD education; and (3) eight sessions of oncology nurse-delivered telephone counselling with DVD education. Two intervention sessions will be delivered before surgery and six over the six months post-surgery. The intervention will utilise a cognitive behavioural approach along with couple relationship education focussed on relationship enhancement and helping the couple to conjointly manage the stresses of cancer diagnosis and treatment. Participants will be assessed at baseline (before surgery) and 3, 6 and 12 months post-surgery. Outcome measures include: Sexual adjustment; unmet sexuality supportive care needs; attitudes to sexual help seeking; psychological adjustment; benefit finding and quality of life. Discussion: The study will provide recommendations about the efficacy of peer support vs. nurse counselling to facilitate better sexual and couple adjustment after prostate cancer as well as recommendations on whether the interventions represent efficient health service delivery

Analgesic and Anti-Inflammatory Effects of the Novel Semicarbazide-Sensitive Amine-Oxidase Inhibitor SzV-1287 in Chronic Arthritis Models of the Mouse.

Semicarbazide-sensitive amine oxidase (SSAO) catalyses oxidative deamination of primary amines. Since there is no data about its function in pain and arthritis mechanisms, we investigated the effects of our novel SSAO inhibitor SzV-1287 in chronic mouse models of joint inflammation. Effects of SzV-1287 (20 mg/kg i.p./day) were investigated in the K/BxN serum-transfer and complete Freund's adjuvant (CFA)-evoked active immunization models compared to the reference SSAO inhibitor LJP-1207. Mechanonociception was assessed by aesthesiometry, oedema by plethysmometry, clinical severity by scoring, joint function by grid test, myeloperoxidase activity by luminescence, vascular leakage by fluorescence in vivo imaging, histopathological changes by semiquantitative evaluation, and cytokines by Luminex assay. SzV-1287 significantly inhibited hyperalgesia and oedema in both models. Plasma leakage and keratinocyte chemoattractant production in the tibiotarsal joint, but not myeloperoxidase activity was significantly reduced by SzV-1287 in K/BxN-arthritis. SzV-1287 did not influence vascular and cellular mechanisms in CFA-arthritis, but significantly decreased histopathological alterations. There was no difference in the anti-hyperalgesic and anti-inflammatory actions of SzV-1287 and LJP-1207, but only SzV-1287 decreased CFA-induced tissue damage. Unlike SzV-1287, LJP-1207 induced cartilage destruction, which was confirmed in vitro. SzV-1287 exerts potent analgesic and anti-inflammatory actions in chronic arthritis models of distinct mechanisms, without inducing cartilage damage

Down-Regulation of Honey Bee IRS Gene Biases Behavior toward Food Rich in Protein

Food choice and eating behavior affect health and longevity. Large-scale research efforts aim to understand the molecular and social/behavioral mechanisms of energy homeostasis, body weight, and food intake. Honey bees (Apis mellifera) could provide a model for these studies since individuals vary in food-related behavior and social factors can be controlled. Here, we examine a potential role of peripheral insulin receptor substrate (IRS) expression in honey bee foraging behavior. IRS is central to cellular nutrient sensing through transduction of insulin/insulin-like signals (IIS). By reducing peripheral IRS gene expression and IRS protein amount with the use of RNA interference (RNAi), we demonstrate that IRS influences foraging choice in two standard strains selected for different food-hoarding behavior. Compared with controls, IRS knockdowns bias their foraging effort toward protein (pollen) rather than toward carbohydrate (nectar) sources. Through control experiments, we establish that IRS does not influence the bees' sucrose sensory response, a modality that is generally associated with food-related behavior and specifically correlated with the foraging preference of honey bees. These results reveal a new affector pathway of honey bee social foraging, and suggest that IRS expressed in peripheral tissue can modulate an insect's foraging choice between protein and carbohydrate sources

Synergies, Strengths and Challenges: Findings on Community Capability from a Systematic Health Systems Research Literature Review

Background: Community capability is the combined influence of a community’s social systems and collective resources that can address community problems and broaden community opportunities. We frame it as consisting of three domains that together support community empowerment: what communities have; how communities act; and for whom communities act. We sought to further understand these domains through a secondary analysis of a previous systematic review on community participation in health systems interventions in low and middle income countries (LMICs). Methods: We searched for journal articles published between 2000 and 2012 related to the concepts of “community”, “capability/participation”, “health systems research” and “LMIC.” We identified 64 with rich accounts of community participation involving service delivery and governance in health systems research for thematic analysis following the three domains framing community capability. Results: When considering what communities have, articles reported external linkages as the most frequently gained resource, especially when partnerships resulted in more community power over the intervention. In contrast, financial assets were the least mentioned, despite their importance for sustainability. With how communities act, articles discussed challenges of ensuring inclusive participation and detailed strategies to improve inclusiveness. Very little was reported about strengthening community cohesiveness and collective efficacy despite their importance in community initiatives. When reviewing for whom communities act, the importance of strong local leadership was mentioned frequently, while conflict resolution strategies and skills were rarely discussed. Synergies were found across these elements of community capability, with tangible success in one area leading to positive changes in another. Access to information and opportunities to develop skills were crucial to community participation, critical thinking, problem solving and ownership. Although there are many quantitative scales measuring community capability, health systems research engaged with community participation has rarely made use of these tools or the concepts informing them. Overall, the amount of information related to elements of community capability reported by these articles was low and often of poor quality. Conclusions: Strengthening community capability is critical to ensuring that community participation leads to genuine empowerment. Our simpler framework to define community capability may help researchers better recognize, support and assess it

Separation of Recombination and SOS Response in Escherichia coli RecA Suggests LexA Interaction Sites

RecA plays a key role in homologous recombination, the induction of the DNA damage response through LexA cleavage and the activity of error-prone polymerase in Escherichia coli. RecA interacts with multiple partners to achieve this pleiotropic role, but the structural location and sequence determinants involved in these multiple interactions remain mostly unknown. Here, in a first application to prokaryotes, Evolutionary Trace (ET) analysis identifies clusters of evolutionarily important surface amino acids involved in RecA functions. Some of these clusters match the known ATP binding, DNA binding, and RecA-RecA homo-dimerization sites, but others are novel. Mutation analysis at these sites disrupted either recombination or LexA cleavage. This highlights distinct functional sites specific for recombination and DNA damage response induction. Finally, our analysis reveals a composite site for LexA binding and cleavage, which is formed only on the active RecA filament. These new sites can provide new drug targets to modulate one or more RecA functions, with the potential to address the problem of evolution of antibiotic resistance at its root

A cross-sectional survey of the knowledge, attitudes and practices regarding tuberculosis among general practitioners working in municipalities with and without asylum centres in eastern Norway

TB survey among Norwegian GPs survey questionnaire NOR: The survey questionnaire in Norwegian. (PDF 208 kb