Comparison of exhaled breath condensate pH using two commercially available devices in healthy controls, asthma and COPD patients

<p>Abstract</p> <p>Background</p> <p>Analysis of exhaled breath condensate (EBC) is a non-invasive method for studying the acidity (pH) of airway secretions in patients with inflammatory lung diseases.</p> <p>Aim</p> <p>To assess the reproducibility of EBC pH for two commercially available devices (portable RTube and non-portable ECoScreen) in healthy controls, patients with asthma or COPD, and subjects suffering from an acute cold with lower-airway symptoms. In addition, we assessed the repeatability in healthy controls.</p> <p>Methods</p> <p>EBC was collected from 40 subjects (n = 10 in each of the above groups) using RTube and ECoScreen. EBC was collected from controls on two separate occasions within 5 days. pH in EBC was assessed after degasification with argon for 20 min.</p> <p>Results</p> <p>In controls, pH-measurements in EBC collected by RTube or ECoScreen showed no significant difference between devices (p = 0.754) or between days (repeatability coefficient RTube: 0.47; ECoScreen: 0.42) of collection. A comparison between EBC pH collected by the two devices in asthma, COPD and cold patients also showed good reproducibility. No differences in pH values were observed between controls (mean pH 8.27; RTube) and patients with COPD (pH 7.97) or asthma (pH 8.20), but lower values were found using both devices in patients with a cold (pH 7.56; RTube, p < 0.01; ECoScreen, p < 0.05).</p> <p>Conclusion</p> <p>We conclude that pH measurements in EBC collected by RTube and ECoScreen are repeatable and reproducible in healthy controls, and are reproducible and comparable in healthy controls, COPD and asthma patients, and subjects with a common cold.</p

Functional Refinement in the Projection from Ventral Cochlear Nucleus to Lateral Superior Olive Precedes Hearing Onset in Rat

Principal neurons of the lateral superior olive (LSO) compute the interaural intensity differences necessary for localizing high-frequency sounds. To perform this computation, the LSO requires precisely tuned, converging excitatory and inhibitory inputs that are driven by the two ears and that are matched for stimulus frequency. In rodents, the inhibitory inputs, which arise from the medial nucleus of the trapezoid body (MNTB), undergo extensive functional refinement during the first postnatal week. Similar functional refinement of the ascending excitatory pathway, which arises in the anteroventral cochlear nucleus (AVCN), has been assumed but has not been well studied. Using whole-cell voltage clamp in acute brainstem slices of neonatal rats, we examined developmental changes in input strength and pre- and post-synaptic properties of the VCN-LSO pathway. A key question was whether functional refinement in one of the two major input pathways might precede and then guide refinement in the opposite pathway. We find that elimination and strengthening of VCN inputs to the LSO occurs over a similar period to that seen for the ascending inhibitory (MNTB-LSO) pathway. During this period, the fractional contribution provided by NMDA receptors (NMDARs) declines while the contribution from AMPA receptors (AMPARs) increases. In the NMDAR-mediated response, GluN2B-containing NMDARs predominate in the first postnatal week and decline sharply thereafter. Finally, the progressive decrease in paired-pulse depression between birth and hearing onset allows these synapses to follow progressively higher frequencies. Our data are consistent with a model in which the excitatory and inhibitory projections to LSO are functionally refined in parallel during the first postnatal week, and they further suggest that GluN2B-containing NMDARs may mediate early refinement in the VCN-LSO pathway

Effect of allergen-specific immunotherapy with purified Alt a1 on AMP responsiveness, exhaled nitric oxide and exhaled breath condensate pH: a randomized double blind study

<p>Abstract</p> <p>Background</p> <p>Little information is available on the effect of allergen-specific immunotherapy on airway responsiveness and markers in exhaled air. The aims of this study were to assess the safety of immunotherapy with purified natural Alt a1 and its effect on airway responsiveness to direct and indirect bronchoconstrictor agents and markers in exhaled air.</p> <p>Methods</p> <p>This was a randomized double-blind trial. Subjects with allergic rhinitis with or without mild/moderate asthma sensitized to <it>A alternata </it>and who also had a positive skin prick test to Alt a1 were randomized to treatment with placebo (n = 18) or purified natural Alt a1 (n = 22) subcutaneously for 12 months. Bronchial responsiveness to adenosine 5'-monophosphate (AMP) and methacholine, exhaled nitric oxide (ENO), exhaled breath condensate (EBC) pH, and serum Alt a1-specific IgG₄antibodies were measured at baseline and after 6 and 12 months of treatment. Local and systemic adverse events were also registered.</p> <p>Results</p> <p>The mean (95% CI) allergen-specific IgG₄value for the active treatment group increased from 0.07 μg/mL (0.03-0.11) at baseline to 1.21 μg/mL (0.69-1.73, P < 0.001) at 6 months and to 1.62 μg/mL (1.02-2.22, P < 0.001) at 12 months of treatment. In the placebo group, IgG₄value increased nonsignificantly from 0.09 μg/mL (0.06-0.12) at baseline to 0.13 μg/mL (0.07-0.18) at 6 months and to 0.11 μg/mL (0.07-0.15) at 12 months of treatment. Changes in the active treatment group were significantly higher than in the placebo group both at 6 months (P < 0.001) and at 12 months of treatment (P < 0.0001). However, changes in AMP and methacholine responsiveness, ENO and EBC pH levels were not significantly different between treatment groups. The overall incidence of adverse events was comparable between the treatment groups.</p> <p>Conclusion</p> <p>Although allergen-specific immunotherapy with purified natural Alt a1 is well tolerated and induces an allergen-specific IgG₄response, treatment is not associated with changes in AMP or methacholine responsiveness or with significant improvements in markers of inflammation in exhaled air. These findings suggest dissociation between the immunotherapy-induced increase in IgG₄levels and its effect on airway responsiveness and inflammation.</p

ICAR: endoscopic skull‐base surgery

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Dynamic clamp as a tool to study the functional effects of individual membrane currents

Today, the patch-clamp technique is the main technique in electrophysiology to record action potentials or membrane current from isolated cells, using a patch pipette to gain electrical access to the cell. The common recording modes of the patch-clamp technique are current clamp and voltage clamp. In the current clamp mode, the current injected through the patch pipette is under control while the free-running membrane potential of the cell is recorded. Current clamp allows for measurements of action potentials that may either occur spontaneously or in response to an injected stimulus current. In voltage clamp mode, the membrane potential is held at a set level through a feedback circuit, which allows for the recording of the net membrane current at a given membrane potential. A less common configuration of the patch-clamp technique is the dynamic clamp. In this configuration, a specific non-predetermined membrane current can be added to or removed from the cell while it is in free-running current clamp mode. This current may be computed in real time, based on the recorded action potential of the cell, and injected into the cell. Instead of being computed, this current may also be recorded from a heterologous expression system such as a HEK-293 cell that is voltage-clamped by the free-running action potential of the cell (&quot;dynamic action potential clamp&quot;). Thus, one may directly test the effects of an additional or mutated membrane current, a synaptic current or a gap junctional current on the action potential of a patch-clamped cell. In the present chapter, we describe the dynamic clamp on the basis of its application in cardiac cellular electrophysiology