Examining the effects of sodium ions on the binding of antagonists to dopamine D2 and D3 receptors

Many G protein-coupled receptors have been shown to be sensitive to the presence of sodium ions (Na+). Using radioligand competition binding assays, we have examined and compared the effects of sodium ions on the binding affinities of a number of structurally diverse ligands at human dopamine D2 and dopamine D3 receptor subtypes, which are important therapeutic targets for the treatment of psychotic disorders. At both receptors, the binding affinities of the antagonists/inverse agonists SB-277011-A, L,741,626, GR 103691 and U 99194 were higher in the presence of sodium ions compared to those measured in the presence of the organic cation, N-methyl-D-glucamine, used to control for ionic strength. Conversely, the affinities of spiperone and (+)-butaclamol were unaffected by the presence of sodium ions. Interestingly, the binding of the antagonist/inverse agonist clozapine was affected by changes in ionic strength of the buffer used rather than the presence of specific cations. Similar sensitivities to sodium ions were seen at both receptors, suggesting parallel effects of sodium ion interactions on receptor conformation. However, no clear correlation between ligand characteristics, such as subtype selectivity, and sodium ion sensitivity were observed. Therefore, the properties which determine this sensitivity remain unclear. However these findings do highlight the importance of careful consideration of assay buffer composition for in vitro assays and when comparing data from different studies, and may indicate a further level of control for ligand binding in vivo

Chemical cues and pheromones in the sea lamprey (Petromyzon marinus)

Chemical cues and pheromones guide decisions in organisms throughout the animal kingdom. The neurobiology, function, and evolution of olfaction are particularly well described in insects, and resulting concepts have driven novel approaches to pest control. However, aside from several exceptions, the olfactory biology of vertebrates remains poorly understood. One exception is the sea lamprey (Petromyzon marinus), which relies heavily upon olfaction during reproduction. Here, we provide a broad review of the chemical cues and pheromones used by the sea lamprey during reproduction, including overviews of the sea lamprey olfactory system, chemical cues and pheromones, and potential applications to population management. The critical role of olfaction in mediating the sea lamprey life cycle is evident by a well-developed olfactory system. Sea lamprey use chemical cues and pheromones to identify productive spawning habitat, coordinate spawning behaviors, and avoid risk. Manipulation of olfactory biology offers opportunities for management of populations in the Laurentian Great Lakes, where the sea lamprey is a destructive invader. We suggest that the sea lamprey is a broadly useful organism with which to study vertebrate olfaction because of its simple but well-developed olfactory organ, the dominant role of olfaction in guiding behaviors during reproduction, and the direct implications for vertebrate pest management

Motivational Interviewing Improves Medication Adherence: a Systematic Review and Meta-analysis

BACKGROUND: Randomized clinical trials (RCTs), mostly conducted among minority populations, have reported that motivational interviewing (MI) can improve medication adherence. OBJECTIVES: To evaluate the impact of MI and of the MI delivery format, fidelity assessment, fidelity-based feedback, counselors’ background and MI exposure time on adherence. DATA SOURCES: We searched the MEDLINE database for studies published from 1966 until February 2015. STUDY ELIGIBILITY CRITERIA: We included RCTs that compared MI to a control group and reported a numerical measure of medication adherence. DATA SYNTHESIS: The main outcome was medication adherence defined as any subjective or objective measure reported as the proportion of subjects with adequate adherence or mean adherence and standard deviation. For categorical variables we calculated the relative risk (RR) of medication adherence, and for continuous variables we calculated the standardized mean difference (SMD) between the MI and control groups. RESULTS: We included 17 RCTs. Ten targeted adherence to HAART. For studies reporting a categorical measure (n = 11), the pooled RR for medication adherence was higher for MI compared with control (1.17; 95 % CI 1.05- 1.31; p < 0.01). For studies reporting a continuous measure (n = 11), the pooled SMD for medication adherence was positive (0.70; 95 % CI 0.15-1.25; p < 0.01) for MI compared with control. The characteristics that were significantly (p < 0.05) associated with medication adherence were telephonic MI and fidelity-based feedback among studies reporting categorical measures, group MI and fidelity assessment among studies reporting continuous measures and delivery by nurses or research assistants. Effect sizes differed in magnitude, creating high heterogeneity. CONCLUSION: MI improves medication adherence at different exposure times and counselors’ educational level. However, the evaluation of MI characteristics associated with success had inconsistent results. Larger studies targeting diverse populations with a variety of chronic conditions are needed to clarify the effect of different MI delivery modes, fidelity assessment and provision of fidelity based-feedback