128 research outputs found
Upregulation of the voltage-gated sodium channel beta2 subunit in neuropathic pain models: characterization of expression in injured and non-injured primary sensory neurons
The development of abnormal primary sensory neuron excitability and neuropathic pain symptoms after peripheral nerve injury is associated with altered expression of voltage-gated sodium channels (VGSCs) and a modification of sodium currents. To investigate whether the beta2 subunit of VGSCs participates in the generation of neuropathic pain, we used the spared nerve injury (SNI) model in rats to examine beta2 subunit expression in selectively injured (tibial and common peroneal nerves) and uninjured (sural nerve) afferents. Three days after SNI, immunohistochemistry and Western blot analysis reveal an increase in the beta2 subunit in both the cell body and peripheral axons of injured neurons. The increase persists for >4 weeks, although beta2 subunit mRNA measured by real-time reverse transcription-PCR and in situ hybridization remains unchanged. Although injured neurons show the most marked upregulation,beta2 subunit expression is also increased in neighboring non-injured neurons and a similar pattern of changes appears in the spinal nerve ligation model of neuropathic pain. That increased beta2 subunit expression in sensory neurons after nerve injury is functionally significant, as demonstrated by our finding that the development of mechanical allodynia-like behavior in the SNI model is attenuated in beta2 subunit null mutant mice. Through its role in regulating the density of mature VGSC complexes in the plasma membrane and modulating channel gating, the beta2 subunit may play a key role in the development of ectopic activity in injured and non-injured sensory afferents and, thereby, neuropathic pain
Impact of host and environmental factors on β-glucuronidase enzymatic activity: implications for gastrointestinal serotonin
The gastrointestinal tract houses a reservoir of bacterial-derived enzymes which can directly catalyze the metabolism of drugs, dietary elements, and endogenous molecules. Both host and environmental factors may influence this enzymatic activity, with the potential to dictate the availability of the biologically-active form of endogenous molecules in the gut and influence inter-individual variation in drug metabolism. We aimed to investigate the influence of the microbiota, and the modulation of its composition, on fecal enzymatic activity. Intrinsic factors related to the host, including age, sex, and genetic background, were explored. Fecalase, a cell-free extract of feces, was prepared and used in a colorimetric-based assay to quantify enzymatic activity. To demonstrate the functional effects of fecal enzymatic activity, we examined β-glucuronidase-mediated cleavage of serotonin β-D-glucuronide (5-HT-GLU) and the resultant production of free 5-HT by HPLC. As expected, β-glucuronidase and β-glucosidase activity were absent in germ-free mice. Enzymatic activity was significantly influenced by mouse strain and animal species. Sex and age significantly altered metabolic activity with implications for free 5-HT. β-glucuronidase and β-glucosidase activity remained at reduced levels for nearly two weeks after cessation of antibiotic administration. This effect on fecalase corresponded to significantly lower 5-HT levels as compared to incubation with pre-antibiotic fecalase from the same mice. Dietary targeting of the microbiota using prebiotics did not alter β-glucuronidase or β-glucosidase activity. Our data demonstrate that multiple factors influence the activity of bacterial-derived enzymes which may have potential clinical implications for drug metabolism and the deconjugation of host-produced glucuronides in the gut
Snow White Is Missing: An Interactive Locative Story for Dementia Patients
With the increasing prevalence of powerful mobile technology, interactive entertainment is also becoming increasingly mobile. This can also be said for a range of applications including those pertaining to mental and physical health which are also looking to take advantage of the increase in mobile technology to create digital interventions and other treatment based software for mobile devices that can benefit from the mobile deliver form. In this paper we propose a new form of serious game in this vein: therapeutic locative interactive fiction. These are interactive story experiences, read while on the move, that respond to the readers environment and location context, and have therapeutic value. The locative nature of these stories enables therapeutic activities connected with out door spaces, and allows for content to enrich users, the readers of locational context. We present a demonstration of this concept through our own therapeutic locative interactive narrative: Snow White is Missing, and detail both its design from an interactive narrative and therapeutic activity perspectives
Interventions that support the creation of dementia friendly environments in health care : protocol for a realist review
© 2016 Handley et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise statedImproving health-care outcomes for people living with dementia when they are admitted to hospital is a policy priority. Dementia friendly interventions in health care promote inclusion of patients and carers in decision-making and adapt practices and environments to be appropriate to the needs of people with cognitive impairment. While there has been a wealth of activity, the number of studies evaluating interventions is limited, and the majority focuses on reporting staff and organisational outcomes. By focusing on patient and carer outcomes, this review will aim to develop an explanatory account of how and in what circumstances dementia friendly environments in health care work for people living with dementia and with what outcomesPeer reviewe
Ultrastructural changes of the intracellular surfactant pool in a rat model of lung transplantation-related events
<p>Abstract</p> <p>Background</p> <p>Ischemia/reperfusion (I/R) injury, involved in primary graft dysfunction following lung transplantation, leads to inactivation of intra-alveolar surfactant which facilitates injury of the blood-air barrier. The alveolar epithelial type II cells (AE2 cells) synthesize, store and secrete surfactant; thus, an intracellular surfactant pool stored in lamellar bodies (Lb) can be distinguished from the intra-alveolar surfactant pool. The aim of this study was to investigate ultrastructural alterations of the intracellular surfactant pool in a model, mimicking transplantation-related procedures including flush perfusion, cold ischemia and reperfusion combined with mechanical ventilation.</p> <p>Methods</p> <p>Using design-based stereology at the light and electron microscopic level, number, surface area and mean volume of AE2 cells as well as number, size and total volume of Lb were determined in a group subjected to transplantation-related procedures including both I/R injury and mechanical ventilation (I/R group) and a control group.</p> <p>Results</p> <p>After I/R injury, the mean number of Lb per AE2 cell was significantly reduced compared to the control group, accompanied by a significant increase in the luminal surface area per AE2 cell in the I/R group. This increase in the luminal surface area correlated with the decrease in surface area of Lb per AE2. The number-weighted mean volume of Lb in the I/R group showed a tendency to increase.</p> <p>Conclusion</p> <p>We suggest that in this animal model the reduction of the number of Lb per AE2 cell is most likely due to stimulated exocytosis of Lb into the alveolar space. The loss of Lb is partly compensated by an increased size of Lb thus maintaining total volume of Lb per AE2 cell and lung. This mechanism counteracts at least in part the inactivation of the intra-alveolar surfactant.</p
Mathematical Modeling of Watersheds as a Subsidy for Reservoir Water Balance Determination: The Case of Paranoá Lake, Federal District, Brazil
Paranoá Lake, Federal District (DF), Brazil, is one of the most important urban lakes in the country and it receives inputs from basins with different characteristics, from natural and preserved to intensely urbanized and agricultural areas. The study of the hydrological processes in these basins, as well as the water balance in each of them, is fundamental for planning current and future water uses in Paranoá Lake. Using an extensive database (35 years) and the Soil and Water Assessment Tool (SWAT) model, we modelled five sub-basins. The outflow rates of the model for each sub-basin served as input for determining the water balance of Paranoá Lake, which recently became part of the DF public water supply system. Despite extensive flow monitoring in the main lake tributaries, about 20% of the lake basin is composed of direct contribution or non-monitored tributaries. Additionally, the lake outflow is composed of a spillway and a hydropower generation unit that does not have proper flow measurements, and thus a correct basin hydrological simulation is essential for water balance aiming to water management scenarios. The results show an average long-term balance of 18.073 m3/s, with minimum flows around 13 m3/s and maximum flows close to 30 m3/s. This is a pioneering study that associates the extensive monitored database and the hydrological simulation of all affluent basins with the water balance of Paranoá Lake. The results obtained are essential to water management and hydrodynamic modeling of the lake
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