Dopamine signalling in pancreatic islet cells and role in adaptations to metabolic stress.

OBJECTIVES: Dopamine and related receptors are evidenced in pancreatic endocrine tissue, but the impact on islet ß-cell stimulus-secretion as well as (patho)physiological role are unclear. METHODS: The present study has evaluated islet cell signalling pathways and biological effects of dopamine, as well as alterations of islet dopamine in rodent models of diabetes of different aetiology. KEY FINDINGS: The dopamine precursor L-DOPA partially impaired glucose tolerance in mice and attenuated glucose-, exendin-4, and alanine-induced insulin secretion. The latter effect was echoed by the attenuation of glucose-induced [Ca2+]i dynamics and elevation of ATP levels in individual mouse islet cells. L-DOPA significantly decreased ß-cell proliferation rates, acting predominantly via the D2 receptor, which was most abundant at the mRNA level. The administration of streptozotocin (STZ) or high-fat diet (HFD) in mice significantly elevated numbers of dopamine-positive islet cells, with HFD also increasing colocalization of dopamine with insulin. At the same time, colocalization of dopamine with glucagon was increased in STZ-treated and pregnant mice, but unaffected by HFD. CONCLUSION: These findings highlight a role for dopamine receptor signalling in islet cell biology adaptations to various forms of metabolic stress.

Imaging Meets Cytometry: Analyzing Heterogeneous Functional Microscopic Data from Living Cell Populations.

Biological tissue consists of populations of cells exhibiting different responses to pharmacological stimuli. To probe the heterogeneity of cell function, we propose a multiplexed approach based on real-time imaging of the secondary messenger levels within each cell of the tissue, followed by extraction of the changes of single-cell fluorescence over time. By utilizing a piecewise baseline correction, we were able to quantify the effects of multiple pharmacological stimuli added and removed sequentially to pancreatic islets of Langerhans, thereby performing a deep functional profiling for each cell within the islet. Cluster analysis based on the functional profile demonstrated dose-dependent changes in statistical inter-relationships between islet cell populations. We therefore believe that the functional cytometric approach can be used for routine quantitative profiling of the tissue for drug screening or pathological testing.

The therapeutic encounter within the event of forensic psychotherapy: a phenomenological hermeneutic of the givenness of the other within the therapeutic relationship.

In this article, we draw upon the works of Jean-Luc Marion and Claude Romano to offer a phenomenological hermeneutic of clinical forensics. We introduce Marion's description of givenness and the event, and apply these ideas to clinical forensics. First, we describe Romano's conceptualization of the transformative effect of the event, relative to the "openness" of the participants to this encounter. Second, we contextualize different possibilities of therapy relative to the openness and closedness of the therapist and patient.

Identification and characterization of novel sodium/potassium-ATPase inhibitors by virtual screening of a compound database.

The medicinal value of cardiac glycoside inhibitors for the treatment of congestive heart failure symptoms stems from their ability to specifically inhibit the ion transport activity of the transmembrane enzyme sodium/potassium-ATPase (Na/K-ATPase) in myocardial cells. In this study, we used the inhibitory potencies of 39 cardiac glycoside analogues for the development of a quantitative structure-activity relationship (QSAR) model for Na/K-ATPase inhibition. In conjunction with a substructure and similarity search, the QSAR model was used to select ten potential inhibitors from a commercial compound database. The inhibitory potencies of these compounds were measured and four were found to be more active than the commonly used inhibitor ouabain. The results of the bioassays were incorporated into a second QSAR model, whose physical interpretation suggested that the nature of substituents in positions 10, 12, and 17 at the cyclopentanoperhydrophenanthrene core of the inhibitors was critical for enzyme inhibition. All descriptors of the QSAR models were conformation-independent, making the search protocol a suitable tool for the rapid virtual screening of large compound databases for novel inhibitors.

Importance of dynamic surface tension to the residual water content of fabrics.

At the end of the final spin cycle of the laundry process, the residual moisture content (RMC) of fabric is directly related to the dynamic surface tension of the residual water in the fabric. The LaPlace equation for capillary rise predicts that the capillary rise of solutions in a capillary is proportional to the surface tension at the air-liquid interface. If fabric can be considered to be a large ensemble of capillaries due to interfiber spacing, then the RMC of fabrics will be directly related to the surface tension of residual solution in the fabric. The use of a tailored rinse additive has the potential to decrease the surface tension of solution significantly, thus leading to a decrease in the residual water content of the fabric. It is expected that as the surfactant concentration increases the surface tension decreases. Hence, the RMC of fabrics must decrease with increasing surfactant concentration. However, a peak is observed in the RMC of fabrics before the critical micelle concentration (CMC) is reached. Prior to the CMC, it is proposed that a sudden adsorption of surfactant is occurring on the fabric surface leading to a decrease in bulk monomer concentration. The decrease in free monomer concentration should result in an increase in the equilibrium surface tension of the residual solution leading to a concomitant increase in RMC. Because the dynamic surface tension is measured on a short time scale (on the order of milliseconds), there will be less adsorption of monomer onto the newly created air-liquid interface of the bubbles during the measurement process. This decrease in adsorption should lead to a pronounced increase in the dynamic surface tension. This indeed was observed. The RMC correlates very well with the dynamic surface tension of the residual solution.

Counseling utilization by ethnic minority college students.

Although multicultural awareness in counseling has risen substantially in the last decade, little research has examined counseling utilization and outcomes for ethnic minorities on university campuses. A sample of 1,166 African American, Asian American, Caucasian, and Latino help-seeking university students from over 40 universities nationwide filled out the Outcome Questionnaire 45 (OQ45) at the first and last therapy sessions. Caucasian students attended significantly more sessions than all other groups. Greatest distress was found at intake in Asian American students, followed by Latino, African American, and Caucasian students. All groups appeared to benefit from therapy, as noted by a decrease in symptomatology, but none of the groups met the criteria for clinically significant change for the OQ45. Implications for therapists working with minority clients are discussed.