A Modified Laryngeal Stent for Glotto-Subglottic Stenosis: A Novel Stent for Better Outcomes.

Management of laryngotracheal stenosis is challenging and laryngotracheal stenosis is generally managed with laryngotracheal reconstruction. Stents are often used as part of the reconstructive surgery. Although most stents adequately stabilize the reconstruction during healing, they often do a poor job of mimicking glottic anatomy, particularly the anterior glottis. Here, we present a modified suprastomal stent designed to stabilize reconstruction after laryngotracheal reconstruction while also improving postoperative glottic anatomy and function. The case of a 15-year-old tracheostomy-dependent patient with glotto-subglottic stenosis who underwent laryngotracheal reconstruction using this modified stent is described. The patient had an excellent outcome with decannulation of her tracheostomy and significant improvement in voice.

Trichloroethylene (TCE) in tree cores to complement a subsurface investigation on residential property near a former electroplating facility.

Tree cores were collected and analyzed for trichloroethylene (TCE) on a private property between a former electroplating facility in Asheville, North Carolina (USA), and a contaminated wetland/spring complex. TCE was detected in 16 of 31 trees, the locations of which were largely consistent with a "plume core" delineated by a more detailed subsurface investigation nearly 2 years later. Concentrations in tree cores and nearby soil borings were not correlated, perhaps due to heterogeneities in both geologic and tree root structure, spatial and temporal variability in transpiration rates, or interferences caused by other contaminants at the site. Several tree cores without TCE provided evidence for significantly lower TCE concentrations in shallow groundwater along the margins of the contaminated spring complex in an area with limited accessibility. This study demonstrates that tree core analyses can complement a more extensive subsurface investigation, particularly in residential or ecologically sensitive areas.

Chaperone-independent mitochondrial translocation and protection by αB-crystallin in RPE cells.

αB-crystallin is a small heat shock protein that exhibits chaperone activity and can protect multiple cell types against oxidative stress damage. Altered levels and specific mutations of αB-crystallin are associated with multiple degenerative diseases. We previously found that αB-crystallin translocates to lens and retinal cell mitochondria upon oxidative stress exposure where it provides protection against oxidative stress damage. To date, the role of the chaperone function of αB-crystallin in mitochondrial translocation and protection has not been established. Here, we sought to determine the relationship between the chaperone activity of αB-crystallin and its ability to translocate to and protect retinal cell mitochondria against oxidative stress damage. Our data provide evidence that three forms of αB-crystallin exhibiting different chaperone activity levels including wild-type, R120G (decreased chaperone activity) and M68A (increased chaperone activity) provide comparable levels of mitochondrial translocation and protection to retinal cells exposed to oxidative stress. The results provide evidence that mitochondrial translocation and protection by αB-crystallin is independent of its chaperone activity and that other functions of αB-crystallin may also be independent of its chaperone activity.

The role of connexin-36 gap junctions in alcohol intoxication and consumption.

Ventral tegmental area (VTA) GABA neurons appear to be critical substrates underlying the acute and chronic effects of ethanol on dopamine (DA) neurotransmission in the mesocorticolimbic system implicated in alcohol reward. The aim of this study was to examine the role of midbrain connexin-36 (Cx36) gap junctions (GJs) in ethanol intoxication and consumption. Using behavioral, molecular, and electrophysiological methods, we compared the effects of ethanol in mature Cx36 knockout (KO) mice and age-matched wild-type (WT) controls. Compared to WT mice, Cx36 KO mice exhibited significantly more ethanol-induced motor impairment in the open field test, but less disruption in motor coordination in the rotarod paradigm. Cx36 KO mice, and WT mice treated with the Cx36 antagonist mefloquine (MFQ), consumed significantly less ethanol than their WT controls in the drink-in-the-dark procedure. The firing rate of VTA GABA neurons in WT mice was inhibited by ethanol with an IC50 of 0.25 g/kg, while VTA GABA neurons in KO mice were significantly less sensitive to ethanol. Dopamine neuron GABA-mediated sIPSC frequency was reduced by ethanol (30 mM) in WT mice, but not affected in KO mice. Cx36 KO mice evinced a significant up-regulation in DAT and D2 receptors in the VTA, as assessed by quantitative RT-PCR. These findings demonstrate the behavioral relevance of Cx36 GJ-mediated electrical coupling between GABA neurons in mature animals, and suggest that loss of coupling between VTA GABA neurons results in disinhibition of DA neurons, a hyper-DAergic state and lowered hedonic valence for ethanol consumption.

Mefloquine effects on ventral tegmental area dopamine and GABA neuron inhibition: a physiologic role for connexin-36 GAP junctions.

Connexin-36 (Cx36) gap junctions (GJs) appear to be involved in the synchronization of GABA interneurons in many brain areas. We have previously identified a population of Cx36-connected ventral tegmental area (VTA) GABA neurons that may regulate mesolimbic dopamine (DA) neurotransmission, a system implicated in reward from both natural behaviors and drugs of abuse. The aim of this study was to determine the effect mefloquine (MFQ) has on midbrain DA and GABA neuron inhibition, and the role Cx36 GJs play in regulating midbrain VTA DA neuron activity in mice. In brain slices from adolescent wild-type (WT) mice the Cx36-selective GJ blocker mefloquine (MFQ, 25 µM) increased VTA DA neuron sIPSC frequency sixfold, and mIPSC frequency threefold. However, in Cx36 KO mice, MFQ only increased sIPSC and mIPSC frequency threefold. The nonselective GJ blocker carbenoxolone (CBX, 100 µM) increased DA neuron sIPSC frequency twofold in WT mice, did not affect Cx36 KO mouse sIPSCs, and did not affect mIPSCs in WT or Cx36 KO mice. Interestingly, MFQ had no effect on VTA GABA neuron sIPSC frequency. We also examined MFQ effects on VTA DA neuron firing rate and current-evoked spiking in WT and Cx36 KO mice, and found that MFQ decreased WT DA neuron firing rate and current-evoked spiking, but did not alter these measures in Cx36 KO mice. Taken together these findings suggest that blocking Cx36 GJs increases VTA DA neuron inhibition, and that GJs play in key role in regulating inhibition of VTA DA neurons. Synapse, 2011. © 2011 Wiley-Liss, Inc.

Acupuncture inhibits GABA neuron activity in the ventral tegmental area and reduces ethanol self-administration.

BACKGROUND: Withdrawal from chronic ethanol enhances ventral tegmental area (VTA) GABA neuron excitability and reduces mesolimbic dopamine (DA) neurotransmission, which is suppressed by acupuncture at Shenmen (HT7) points (Zhao et al., 2006). The aim of this study was to evaluate the effects of HT7 acupuncture on VTA GABA neuron excitability, ethanol inhibition of VTA GABA neuron firing rate, and ethanol self-administration. A role for opioid receptors (ORs) in ethanol and acupuncture effects is also explored. METHODS: Using electrophysiological methods in mature rats, we evaluated the effects of HT7 stimulation and opioid antagonists on VTA GABA neuron firing rate. Using behavioral paradigms in rats, we evaluated the effects of HT7 stimulation and opioid antagonists on ethanol self-administration using a modification of the sucrose-fading procedure. RESULTS: HT7 stimulation produced a biphasic modulation of VTA GABA neuron firing rate characterized by transient enhancement followed by inhibition and subsequent recovery in 5 minutes. HT7 inhibition of VTA GABA neuron firing rate was blocked by systemic administration of the nonselective µ-opioid receptor antagonist naloxone. HT7 stimulation significantly reduced ethanol suppression of VTA GABA neuron firing rate, which was also blocked by naloxone. HT7 acupuncture reduced ethanol self-administration without affecting sucrose consumption. Systemic administration of the δ-opioid receptor (DOR) antagonist naltrindole blocked ethanol suppression of VTA GABA neuron firing rate and significantly reduced ethanol self-administration without affecting sucrose consumption. CONCLUSIONS: These findings suggest that DOR-mediated opioid modulation of VTA GABA neurons may mediate acupuncture's role in modulating mesolimbic DA release and suppressing the reinforcing effects of ethanol.

Removal of organic wastewater contaminants in septic systems using advanced treatment technologies.

The detection of pharmaceuticals and other organic wastewater contaminants (OWCs) in ground water and surface-water bodies has raised concerns about the possible ecological impacts of these compounds on nontarget organisms. On-site wastewater treatment systems represent a potentially significant route of entry for organic contaminants to the environment. In this study, effluent samples were collected and analyzed from conventional septic systems and from systems using advanced treatment technologies. Six of 13 target compounds were detected in effluent from at least one septic system. Caffeine, paraxanthine, and acetaminophen were the most frequently detected compounds, and estrogenic activity was detected in 14 of 15 systems. The OWC concentrations were significantly lower in effluent after sand filtration (p < 0.01) or aerobic treatment (p < 0.05) as compared with effluent that had not undergone advanced treatment. In general, concentrations in conventional systems were comparable to those measured in previous studies of municipal wastewater treatment plant (WWTP) influent, and concentrations in systems after advanced treatment were comparable to previously measured concentrations in WWTP effluent. These data indicate that septic systems using advanced treatment can reduce OWCs in treated effluent to similar concentrations as municipal WWTPs.

Assessing background ground water chemistry beneath a new unsewered subdivision.

Previous site-specific studies designed to assess the impacts of unsewered subdivisions on ground water quality have relied on upgradient monitoring wells or very limited background data to characterize conditions prior to development. In this study, an extensive monitoring program was designed to document ground water conditions prior to construction of a rural subdivision in south-central Wisconsin. Previous agricultural land use has impacted ground water quality; concentrations of chloride, nitrate-nitrogen, and atrazine ranged from below the level of detection to 296 mg/L, 36 mg/L, and 0.8 microg/L, respectively, and were highly variable from well to well and through time. Seasonal variations in recharge, surface topography, aquifer heterogeneities, surficial loading patterns, and well casing depth explain observed variations in ground water chemistry. This variability would not have been detected if background conditions were determined from only a few monitoring wells or inferred from wells located upgradient of the subdivision site. This project demonstrates the importance of characterizing both ground water quality and chemical variability prior to land-use change to detect any changes once homes are constructed.