Oxygen-glucose deprivation induces ATP release via maxi-anion channels in astrocytes

ATP represents a major gliotransmitter that serves as a signaling molecule for the cross talk between glial and neuronal cells. ATP has been shown to be released by astrocytes in response to a number of stimuli under nonischemic conditions. In this study, using a luciferin-luciferase assay, we found that mouse astrocytes in primary culture also exhibit massive release of ATP in response to ischemic stress mimicked by oxygen-glucose deprivation (OGD). Using a biosensor technique, the local ATP concentration at the surface of single astrocytes was found to increase to around 4 μM. The OGD-induced ATP release was inhibited by Gd3+ and arachidonic acid but not by blockers of volume-sensitive outwardly rectifying Cl− channels, cystic fibrosis transmembrane conductance regulator (CFTR), multidrug resistance-related protein (MRP), connexin or pannexin hemichannels, P2X7 receptors, and exocytotic vesicular transport. In cell-attached patches on single astrocytes, OGD caused activation of maxi-anion channels that were sensitive to Gd3+ and arachidonic acid. The channel was found to be permeable to ATP4− with a permeability ratio of PATP/PCl = 0.11. Thus, it is concluded that ischemic stress induces ATP release from astrocytes and that the maxi-anion channel may serve as a major ATP-releasing pathway under ischemic conditions

A Spoonful of Math Helps the Medicine Go Down: An Illustration of How Healthcare can Benefit from Mathematical Modeling and Analysis

<p>Abstract</p> <p>Objectives</p> <p>A recent joint report from the Institute of Medicine and the National Academy of Engineering, highlights the benefits of--indeed, the need for--mathematical analysis of healthcare delivery. Tools for such analysis have been developed over decades by researchers in Operations Research (OR). An OR perspective typically frames a complex problem in terms of its essential mathematical structure. This article illustrates the use and value of the tools of operations research in healthcare. It reviews one OR tool, queueing theory, and provides an illustration involving a hypothetical drug treatment facility.</p> <p>Method</p> <p>Queueing Theory (QT) is the study of waiting lines. The theory is useful in that it provides solutions to problems of waiting and its relationship to key characteristics of healthcare systems. More generally, it illustrates the strengths of modeling in healthcare and service delivery.</p> <p>Queueing theory offers insights that initially may be hidden. For example, a queueing model allows one to incorporate randomness, which is inherent in the actual system, into the mathematical analysis. As a result of this randomness, these systems often perform much worse than one might have guessed based on deterministic conditions. Poor performance is reflected in longer lines, longer waits, and lower levels of server utilization.</p> <p>As an illustration, we specify a queueing model of a representative drug treatment facility. The analysis of this model provides mathematical expressions for some of the key performance measures, such as average waiting time for admission.</p> <p>Results</p> <p>We calculate average occupancy in the facility and its relationship to system characteristics. For example, when the facility has 28 beds, the average wait for admission is 4 days. We also explore the relationship between arrival rate at the facility, the capacity of the facility, and waiting times.</p> <p>Conclusions</p> <p>One key aspect of the healthcare system is its complexity, and policy makers want to design and reform the system in a way that affects competing goals. OR methodologies, particularly queueing theory, can be very useful in gaining deeper understanding of this complexity and exploring the potential effects of proposed changes on the system without making any actual changes.</p

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Factors Associated with the Proximity of the Incisive Canal to the Maxillary Central Incisor

The position of the maxillary central incisors (MCIs) is an important factor in treatment planning since it is related to esthetics and physiological function. This study aimed to evaluate maxillofacial morphology related to the proximity of the MCI to the incisive canal (IC) using cone-beam computed tomography (CBCT). In 157 patients, the distance between the MCI and IC was measured using CBCT images, and the maxillofacial morphology was measured using cephalograms. The relationship between age, sex, and cephalometric analysis was subsequently investigated using stepwise multiple regression analysis, with the distance between the MCI root apex and IC as the objective variable, and age, sex, and cephalometric variables as explanatory variables. The results demonstrated significant associations between the distance separating point A and the pterygomaxillary fissure projected on the palatal plane (B = 0.092, p p p = 0.031). Age and sex showed no association with the distance between the IC and MCI. Particular attention should be paid to the proximity of the tooth root to the IC in patients with short anteroposterior diameters of the maxilla and an anterior labial tilt of the dolichofacial type

Chewing Prevents Stress-Induced Hippocampal LTD Formation and Anxiety-Related Behaviors: A Possible Role of the Dopaminergic System

The present study examined the effects of chewing on stress-induced long-term depression (LTD) and anxiogenic behavior. Experiments were performed in adult male rats under three conditions: restraint stress condition, voluntary chewing condition during stress, and control condition without any treatments except handling. Chewing ameliorated LTD development in the hippocampal CA1 region. It also counteracted the stress-suppressed number of entries to the center region of the open field when they were tested immediately, 30 min, or 60 min after restraint. At the latter two poststress time periods, chewing during restraint significantly increased the number of times of open arm entries in the elevated plus maze, when compared with those without chewing. The in vivo microdialysis further revealed that extracellular dopamine concentration in the ventral hippocampus, which is involved in anxiety-related behavior, was significantly greater in chewing rats than in those without chewing from 30 to 105 min after stress exposure. Development of LTD and anxiolytic effects ameliorated by chewing were counteracted by administering the D1 dopamine receptor antagonist SCH23390, which suggested that chewing may activate the dopaminergic system in the ventral hippocampus to suppress stress-induced anxiogenic behavior

Comparison of the Observation Errors of Augmented and Spatial Reality Systems

Using 3D technologies such as virtual reality (VR) and augmented reality (AR), has intensified nowadays. The mainstream AR devices in use today are head-mounted displays (HMDs), which, due to specification limitations, may not perform to their full potential within a distance of 1.0 m. The spatial reality display (SRD) is another system that facilitates stereoscopic vision by the naked eye. The recommended working distance is 30.0~75.0 cm. It is crucial to evaluate the observation accuracy within 1.0 m for each device in the medical context. Here, 3D-CG models were created from dental models, and the observation errors of 3D-CG models displayed within 1.0 m by HMD and SRD were verified. The measurement error results showed that the HMD model yielded more significant results than the control model (Model) under some conditions, while the SRD model had the same measurement accuracy as the Model. The measured errors were 0.29~1.92 mm for HMD and 0.02~0.59 mm for SRD. The visual analog scale scores for distinctness were significantly higher for SRD than for HMD. Three-dimensionality did not show any relationship with measurement error. In conclusion, there is a specification limitation for using HMDs within 1.0 m, as shown by the measured values. In the future, it will be essential to consider the characteristics of each device in selecting the use of AR devices. Here, we evaluated the accuracies of 3D-CG models displayed in space using two different systems of AR devices