499 research outputs found

    Presynaptic action of neurotensin on dopamine release through inhibition of D2 receptor function

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    <p>Abstract</p> <p>Background</p> <p>Neurotensin (NT) is known to act on dopamine (DA) neurons at the somatodendritic level to regulate cell firing and secondarily enhance DA release. In addition, anatomical and indirect physiological data suggest the presence of NT receptors at the terminal level. However, a clear demonstration of the mechanism of action of NT on dopaminergic axon terminals is lacking. We hypothesize that NT acts to increase DA release by inhibiting the function of terminal D2 autoreceptors. To test this hypothesis, we used fast-scan cyclic voltammetry (FCV) to monitor in real time the axonal release of DA in the nucleus accumbens (NAcc).</p> <p>Results</p> <p>DA release was evoked by single electrical pulses and pulse trains (10 Hz, 30 pulses). Under these two stimulation conditions, we evaluated the characteristics of DA D<sub>2 </sub>autoreceptors and the presynaptic action of NT in the NAcc shell and shell/core border region. The selective agonist of D<sub>2 </sub>autoreceptors, quinpirole (1 μM), inhibited DA overflow evoked by both single and train pulses. In sharp contrast, the selective D<sub>2 </sub>receptor antagonist, sulpiride (5 μM), strongly enhanced DA release triggered by pulse trains, without any effect on DA release elicited by single pulses, thus confirming previous observations. We then determined the effect of NT (8–13) (100 nM) and found that although it failed to increase DA release evoked by single pulses, it strongly enhanced DA release evoked by pulse trains that lead to prolonged DA release and engage D<sub>2 </sub>autoreceptors. In addition, initial blockade of D<sub>2 </sub>autoreceptors by sulpiride considerably inhibited further facilitation of DA release generated by NT (8–13).</p> <p>Conclusion</p> <p>Taken together, these data suggest that NT enhances DA release principally by inhibiting the function of terminal D<sub>2 </sub>autoreceptors and not by more direct mechanisms such as facilitation of terminal calcium influx.</p

    Scalable Environment for Quantification of Uncertainty and Optimization in Industrial Applications (SEQUOIA)

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143027/1/6.2017-1327.pd

    Structure-Function Correlation of the Human Central Retina

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    The impact of retinal pathology detected by high-resolution imaging on vision remains largely unexplored. Therefore, the aim of the study was to achieve high-resolution structure-function correlation of the human macula in vivo.To obtain high-resolution tomographic and topographic images of the macula spectral-domain optical coherence tomography (SD-OCT) and confocal scanning laser ophthalmoscopy (cSLO), respectively, were used. Functional mapping of the macula was obtained by using fundus-controlled microperimetry. Custom software allowed for co-registration of the fundus mapped microperimetry coordinates with both SD-OCT and cSLO datasets. The method was applied in a cross-sectional observational study of retinal diseases and in a clinical trial investigating the effectiveness of intravitreal ranibizumab in macular telangietasia type 2. There was a significant relationship between outer retinal thickness and retinal sensitivity (p<0.001) and neurodegeneration leaving less than about 50 µm of parafoveal outer retinal thickness completely abolished light sensitivity. In contrast, functional preservation was found if neurodegeneration spared the photoreceptors, but caused quite extensive disruption of the inner retina. Longitudinal data revealed that small lesions affecting the photoreceptor layer typically precede functional detection but later cause severe loss of light sensitivity. Ranibizumab was shown to be ineffective to prevent such functional loss in macular telangietasia type 2.Since there is a general need for efficient monitoring of the effectiveness of therapy in neurodegenerative diseases of the retina and since SD-OCT imaging is becoming more widely available, surrogate endpoints derived from such structure-function correlation may become highly relevant in future clinical trials

    Referral Physicians’ Knowledge of Radiation Dose: A Cross-sectional Study

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    AIM: The purpose of the study was to evaluate the knowledge of referring physicians of general practitioners, residents, and medical specialists in Jordan and the Middle East on radiation dose and its impact on vulnerable patients. MATERIALS AND METHODS: The Institutional Review Board approved this study before data collection. A cross-sectional study employed questionnaire that was distributed to respondents (n = 293) of general practitioners, residents, specialists, and therapists. The questionnaire consisted of 29 questions. Nine questions concerned with demographics and the remaining 20 questions were divided into five sections: Radiation dose, ionizing radiation, pediatric radiation, pregnant women radiation, and radiation risks. The mean score was computed out of 20. Chi-squared test of independence was utilized to analyze each question. To compare the responses between the demographic variables groups, Kruskal–Wallis and Mann–Whitney tests were used. RESULTS: Out of the 293 respondents, 128 (43.7%) were aware of radiation. The average score of the questionnaire was 9.5 out of 20 (47.5%). Within each section, the level of knowledge varied. Physicians had the highest level of knowledge in radiation risk (85.7%) followed by ionizing radiation (62.1%). The questionnaire revealed lower levels of knowledge in the areas of pediatric radiation, pregnant women radiation, and radiation dose. The percentages of respondents, (with fair to good level of knowledge), were 47.1%, 34.5%, and 24.6%, respectively. CONCLUSION: The results of this study were consistent with previous studies that demonstrated a poor level of general knowledge in referring physicians regarding radiation dose, ionizing radiation, pediatric radiation, pregnant women radiation, and radiation risks
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