Infliximab-Induced Vanishing Bile Duct Syndrome.

Drug-induced liver injury (DILI) is a spectrum of pathology that can be classified by mechanism of injury or by type of observed hepatotoxicity. Vanishing bile duct syndrome (VBDS) is a group of acquired and genetic disorders that cause the destruction and disappearance of intrahepatic bile ducts, and cholestasis. VBDS typically presents with severe cholestatic hepatitis and can have immunoallergic features. Infliximab has been reported to rarely cause a cholestatic pattern of liver injury due to ductopenia characteristic of VBDS. Herein we present a clinical case of infliximab-induced DILI resulting in VBDS.

An Innovative Approach to Adequate Oral Hydration in an Inpatient Geriatric Psychiatry Unit.

Suboptimal hydration status and dehydration are problems that often exacerbate comorbid conditions in geriatric patients. At a Veterans Administration Hospital, it was observed that suboptimal hydration status in Veterans hospitalized in the geriatric psychiatry unit was a contributing factor in the worsening of their psychiatric and medical conditions. A quality improvement project was chartered to improve hydration in this group of patients. Using a three-pronged intervention approach (i.e., providing flavored water, providing larger cups, and increasing the prompting by nurses for patients to drink more), the project was successful. The goal was to increase average daily fluid intake by 125 mL; the result was an increase of 700 mL. This project has been sustained and the interventions have also benefitted non-geriatric psychiatry in-patients. [Journal of Psychosocial Nursing and Mental Health Services, 57(4), 15-20.].

Activation of retinal glial (Müller) cells by extracellular ATP induces pronounced increases in extracellular H+ flux.

Small alterations in extracellular acidity are potentially important modulators of neuronal signaling within the vertebrate retina. Here we report a novel extracellular acidification mechanism mediated by glial cells in the retina. Using self-referencing H+-selective microelectrodes to measure extracellular H+ fluxes, we show that activation of retinal Müller (glial) cells of the tiger salamander by micromolar concentrations of extracellular ATP induces a pronounced extracellular H+ flux independent of bicarbonate transport. ADP, UTP and the non-hydrolyzable analog ATPγs at micromolar concentrations were also potent stimulators of extracellular H+ fluxes, but adenosine was not. The extracellular H+ fluxes induced by ATP were mimicked by the P2Y1 agonist MRS 2365 and were significantly reduced by the P2 receptor blockers suramin and PPADS, suggesting activation of P2Y receptors. Bath-applied ATP induced an intracellular rise in calcium in Müller cells; both the calcium rise and the extracellular H+ fluxes were significantly attenuated when calcium re-loading into the endoplasmic reticulum was inhibited by thapsigargin and when the PLC-IP3 signaling pathway was disrupted with 2-APB and U73122. The anion transport inhibitor DIDS also markedly reduced the ATP-induced increase in H+ flux while SITS had no effect. ATP-induced H+ fluxes were also observed from Müller cells isolated from human, rat, monkey, skate and lamprey retinae, suggesting a highly evolutionarily conserved mechanism of potential general importance. Extracellular ATP also induced significant increases in extracellular H+ flux at the level of both the outer and inner plexiform layers in retinal slices of tiger salamander which was significantly reduced by suramin and PPADS. We suggest that the novel H+ flux mediated by ATP-activation of Müller cells and of other glia as well may be a key mechanism modulating neuronal signaling in the vertebrate retina and throughout the brain.

Extracellular H+ fluxes from tiger salamander Müller (glial) cells measured using self-referencing H+-selective microelectrodes.

Self-referencing H+-selective electrodes were used to measure extracellular H+ fluxes from Müller (glial) cells isolated from the tiger salamander retina. A novel chamber enabled stable recordings using H+-selective microelectrodes in a self-referencing format using bicarbonate-based buffer solutions. A small basal H+ flux was observed from the end foot region of quiescent cells bathed in 24 mM bicarbonate-based solutions, and increasing extracellular potassium induced a dose-dependent increase in H+ flux. Barium at 6 mM also increased H+ flux. Potassium-induced extracellular acidifications were abolished when bicarbonate was replaced by 1 mM HEPES. The carbonic anhydrase antagonist benzolamide potentiated the potassium-induced extracellular acidification, while 300 µM DIDS, 300 µM SITS, and 30 µM S0859 significantly reduced the response. Potassium-induced extracellular acidifications persisted in solutions lacking extracellular calcium, although potassium-induced changes in intracellular calcium monitored with Oregon Green were abolished. Exchange of external sodium with choline also eliminated the potassium-induced extracellular acidification. Removal of extracellular sodium by itself induced a transient alkalinization, and replacement of sodium induced a transient acidification, both of which were blocked by 300 µM DIDS. Recordings at the apical portion of the cell showed smaller potassium-induced extracellular H+ fluxes, and removal of the end foot region further decreased the H+ flux, suggesting that the end foot was the major source of acidifications. These studies demonstrate that self-referencing H+-selective electrodes can be used to monitor H+ fluxes from retinal Müller cells in bicarbonate-based solutions and confirm the presence of a sodium-coupled bicarbonate transporter, the activity of which is largely restricted to the end foot of the cell.NEW & NOTEWORTHY The present study uses self-referencing H+-selective electrodes for the first time to measure H+ fluxes from Müller (glial) cells isolated from tiger salamander retina. These studies demonstrate bicarbonate transport as a potent regulator of extracellular levels of acidity around Müller cells and point toward a need for further studies aimed at addressing how such glial cell pH regulatory mechanisms may shape neuronal signaling.

Euler equation existence, non-uniqueness and mesh converged statistics.

We review existence and non-uniqueness results for the Euler equation of fluid flow. These results are placed in the context of physical models and their solutions. Non-uniqueness is in direct conflict with the purpose of practical simulations, so that a mitigating strategy, outlined here, is important. We illustrate these issues in an examination of mesh converged turbulent statistics, with comparison to laboratory experiments.