21 research outputs found

    5-hydroxytryptamine (5-HT) cellular sequestration during chronic exposure delays 5-HT<sub>3</sub> receptor resensitization due to Its subsequent release

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    The serotonergic synapse is dynamically regulated by serotonin (5-hydroxytryptamine (5-HT)) with elevated levels leading to the down-regulation of the serotonin transporter and a variety of 5-HT receptors, including the 5-HT type-3 (5-HT(3)) receptors. We report that recombinantly expressed 5-HT(3) receptor binding sites are reduced by chronic exposure to 5-HT (IC(50) of 154.0 ± 45.7 Όm, t(œ) = 28.6 min). This is confirmed for 5-HT(3) receptor-induced contractions in the guinea pig ileum, which are down-regulated after chronic, but not acute, exposure to 5-HT. The loss of receptor function does not involve endocytosis, and surface receptor levels are unaltered. The rate and extent of down-regulation is potentiated by serotonin transporter function (IC(50) of 2.3 ± 1.0 Όm, t(œ) = 3.4 min). Interestingly, the level of 5-HT uptake correlates with the extent of down-regulation. Using TX-114 extraction, we find that accumulated 5-HT remains soluble and not membrane-bound. This cytoplasmically sequestered 5-HT is readily releasable from both COS-7 cells and the guinea pig ileum. Moreover, the 5-HT level released is sufficient to prevent recovery from receptor desensitization in the guinea pig ileum. Together, these findings suggest the existence of a novel mechanism of down-regulation where the chronic release of sequestered 5-HT prolongs receptor desensitization

    A Third Measure-Metastable State in the Dynamics of Spontaneous Shape Change in Healthy Human's White Cells

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    Human polymorphonuclear leucocytes, PMN, are highly motile cells with average 12-15 ”m diameters and prominent, loboid nuclei. They are produced in the bone marrow, are essential for host defense, and are the most populous of white blood cell types. PMN also participate in acute and chronic inflammatory processes, in the regulation of the immune response, in angiogenesis, and interact with tumors. To accommodate these varied functions, their behavior is adaptive, but still definable in terms of a set of behavioral states. PMN morphodynamics have generally involved a non-equilibrium stationary, spheroid Idling state that transitions to an activated, ellipsoid translocating state in response to chemical signals. These two behavioral shape-states, spheroid and ellipsoid, are generally recognized as making up the vocabulary of a healthy PMN. A third, “random” state has occasionally been reported as associated with disease states. I have observed this third, Treadmilling state, in PMN from healthy subjects, the cells demonstrating metastable dynamical behaviors known to anticipate phase transitions in mathematical, physical, and biological systems. For this study, human PMN were microscopically imaged and analyzed as single living cells. I used a microscope with a novel high aperture, cardioid annular condenser with better than 100 nanometer resolution of simultaneous, mixed dark field and intrinsic fluorescent images to record shape changes in 189 living PMNs. Relative radial roundness, R(t), served as a computable order parameter. Comparison of R(t) series of 10 cells in the Idling and 10 in the Treadmilling state reveals the robustness of the “random” appearing Treadmilling state, and the emergence of behaviors observed in the neighborhood of global state transitions, including increased correlation length and variance (divergence), sudden jumps, mixed phases, bimodality, power spectral scaling and temporal slowing. Wavelet transformation of an R(t) series of an Idling to Treadmilling state change, demonstrated behaviors concomitant with the observed transition

    Estimating the number of children of parents who misuse substances, including alcohol across the communities of the Tallaght Drug and Alcohol Task Force (TDATF) region.

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    In March 2015 the Tallaght Drugs and Alcohol Task Force (TDATF), in conjunction with Barnardos Lorien Child and Family Service, commissioned research to collect and collate comprehensive and robust data on the number of children potentially affected by parental substance misuse in the communities served by TDATF. The research was undertaken in an effort to provide a better picture of the hidden harm to children of parental substance misuse, in order to plan for local service provision. The objectives of the research were: ‱ To ascertain the potential scale of ‘hidden harm’ to children whose parents misuse substances; ‱ To deliver a comprehensive and robust snapshot of the number of children possibly impacted in the area, so as to inform the development and implementation of the Tallaght Drugs and Alcohol Task Force strategic plan and broader national policy; ‱ To deliver a comprehensive research findings report; and ‱ To make recommendations to progress this area of work and addressing emerging needs. The research design was predominantly quantitative in nature, complemented with a qualitative component. The data collected was analysed, with key findings informing a series of recommendations

    The healthy addiction treatment recovery model: developing a client-driven, nurse-led addiction nursing model.

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    ABSTRACT The current model of nursing within international addiction services has been described as task oriented and reactive. Yet, it is known that nursing models should be led by client need and operate within the domain of the client and their wider environment. The aim of this study was to address this gap within addiction nursing and to develop an evidence-based addiction nursing model. To objectively assess the needs of clients, a cross-sectional survey was implemented within a representative selection of six drug treatment clinics and a sample of clients in receipt of opiate agonist treatment in Dublin, Ireland. The Opiate Treatment Index with the General Health Questionnaire embedded was used to measure heroin use, polydrug use, infectious disease risk, physical health, psychological adjustment, criminality and social well-being. To develop the addiction model, a mapping of relevant features of potential nursing models was conducted by nurses working in addiction services. The key finding from the client assessments was a lack of psychological adjustment; a cutoff score of 4 was recommended. The mean score among women was 11 (95% CI [8, 14]), and that among men was 8 (95% CI [6, 10]). Findings from the mapping of models highlighted the benefits of the BRENDA, FRAMES, and Tidal models. A focus on practical implementation and measurable outcomes was stressed. Results informed the development of the Healthy Addiction Treatment Recovery Model. The model refocused services on clients' objective needs and eradicated entrenched practices

    Clients' views on the importance of a nurse-led approach and nurse prescribing in the development of the healthy addiction treatment recovery model.

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    Globally, from America to Europe and beyond, the need for the expansion of the role of nurse practitioners has been recognized within the healthcare professions. However, little emphasis has been placed on assessing the views of clients, and within the addiction services, the voice of clients can be additionally marginalized as a result of treatment philosophies, stigma, and resource constraints. The aims of this study were to establish from clients their nursing needs and to use these findings alongside an objective measurement of clients' health, to inform the development of a nurse-led treatment model. A cross-sectional survey with open-ended questions on client nursing needs was conducted in 2017 within a representative sample of six clinics in Dublin, Ireland. A convenience sample of 131 clients were interviewed. Interviews were analyzed using thematic analysis. Findings were both as expected and surprising. Clients articulated the role of the nurse in their physical care; however, unexpectedly, clients identified nurses as an essential source of psychological support and expressed the wish for the role to be expanded in terms of managing methadone treatment and accessing additional services and resources.Results contributed to the formation of the nurse-led, client mental-health-focused, Healthy Addiction Treatment Recovery Model for addiction nursing services. In terms of national policies, findings provided new evidence articulated by service users on their desire for the expansion of nurse prescribing in addiction services and an expansion of the role to more adequately address client needs
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