Journal of young investigators最新文献

It has been shown that inhaled particulate matter such as air pollution and asbestos are linked to a number of immune diseases such as asthma, and Systemic Lupus Erythematosus (SLE), respectively. This research may contribute to understanding the mechanisms of how asbestos and air pollution particulate (PM10) produce oxidative stress on macrophages, as well as how the macrophages will respond to the oxidative stressors. Using Flow Cytometry, DCFDA Fluorescence, Glutamate Transport, and Cytokine Bead Array assays, we have shown that exposure to asbestos and PM10 up-regulates system x(c)- in macrophages, which reduces oxidative stress for the macrophage by providing substrates for antioxidants. The results demonstrate that asbestos, but not PM10, induces both expression and activity of system x(c)-. This led to differential cytokine production with a significantly increased expression of TNF alpha and MCP-1 for PM10 treatment but not for asbestos treatment. Inhibition of system x(c)- affected cytokine production only following asbestos exposure, further demonstrating a role for this antioxidant system in regulating immune outcomes for asbestos but not PM10. Understanding the mechanisms in which oxidative stress helps regulate macrophage responses may contribute to a better understanding of why certain diseases are brought on by asbestos and air pollution exposure.

Sensorimortor gating and locomotion are behaviors that reflect pre-attentive sensory filtering and higher order, top-down, sensory processing, respectively. These processes are thought to affect either the perception of novelty in an environment (filtering) or cognition (higher order processing), salient features of models of altered states of consciousness (ASC). Drugs with highly selective receptor affinities that produce ASC can help to establish neural correlates, pathways, and mechanisms underlying ASC. Furthermore, screening for substances that selectively reverse drug-induced sensory processing departures is valuable for development of experimental antipsychotics. This study investigated the anomalous opioid sub-type, the kappa opioid (KA) system, within the two ASC models. Significant interaction and reversal effects between KA and the serotonin/2A (5-HT2A) system - the serotonin sub-type associated with classical psychedelics - were observed in three BPM measures. These measures showed that KA activation-induced effects could be reversed by 5-HT2A deactivation. These results suggest that KA could function as an atypical antipsychotic medications and/or as a screening tool for new antipsychotic medicines. The experimental work for this study comprised dose-response and reversal experiments with drugs that activate and deactivate kappa opioid and serotonin systems in the two behavioral models for the first time in mice.

Aims: Urinary tract obstruction is a common clinical problem involving narrowing anywhere along the ureters or urethra. Current diagnostic methods are invasive and costly, and urologists are constantly seeking new, inexpensive, non-invasive measures to diagnose obstruction. The present study investigates diagnostic applications of computational fluid dynamics (CFD) to urinary tract obstruction for the first time.

Methods: Various hypothetical models were initially created in Gambit 2.1.6, in which the physics of flow was evaluated based on varying geometries and conditions. These models presented short segments of the tract and possible effects of obstruction. Flow analysis was conducted in Fluent 6.1.22 by comparing contours of velocity, static pressure, dynamic pressure, total pressure, and wall shear stress to results predicted by flow theory. Realistic models of both healthy and obstructed urethras and ureters were then similarly created and simulated.

Results: CFD equations accurately predicted the expected flow characteristics through both hypothetical and realistic models. Comparison of modeled urethral outlet velocity to human uroflowmetry data shows that the simulated conditions are almost identical to realistic human flow.

Conclusions: The accuracy of the models suggests clinical potential of using CFD with current techniques in human tract analysis, secondary flow effects, disease prevention, and non-invasive diagnosis.