DCEBIO stimulates Cl−secretion in the mouse jejunum

2006 ◽  
Vol 290 (1) ◽  
pp. C152-C164 ◽  
Author(s):  
Kirk L. Hamilton ◽  
Matt Kiessling

We investigated the effects of 5,6-dichloro-1-ethyl-1,3-dihydro-2 H-benzimidazol-2-one(DCEBIO) on the Cl−secretory response of the mouse jejunum using the Ussing short-circuit current ( Isc) technique. DCEBIO stimulated a concentration-dependent, sustained increase in Isc(EC5041 ± 1 μM). Pretreating tissues with 0.25 μM forskolin reduced the concentration-dependent increase in Iscby DCEBIO and increased the EC50(53 ± 5 μM). Bumetanide blocked (82 ± 5%) the DCEBIO-stimulated Iscconsistent with Cl−secretion. DCEBIO was a more potent stimulator of Cl−secretion than its parent molecule, 1-ethyl-2-benzimidazolinone. Glibenclamide or NPPB reduced the DCEBIO-stimulated Iscby >80% indicating the participation of CFTR in the DCEBIO-stimulated Iscresponse. Clotrimazole reduced DCEBIO-stimulated Iscby 67 ± 15%, suggesting the participation of the intermediate conductance Ca2+-activated K+channel (IKCa) in the DCEBIO-activated Iscresponse. In the presence of maximum forskolin (10 μM), the DCEBIO response was reduced and biphasic, reaching a peak response of the change in Iscof 43 ± 5 μA/cm2and then falling to a steady-state response of 17 ± 10 μA/cm2compared with DCEBIO control tissues (61 ± 6 μA/cm2). The forskolin-stimulated Iscin the presence of DCEBIO was reduced compared with forskolin control tissues. Similar results were observed with DCEBIO and 8-BrcAMP where adenylate cyclase was bypassed. H89, a PKA inhibitor, reduced the DCEBIO-activated Isc, providing evidence that DCEBIO increased Cl−secretion via a cAMP/PKA-dependent manner. These data suggest that DCEBIO stimulates Cl−secretion of the mouse jejunum and that DCEBIO targets components of the Cl−secretory mechanism.

1998 ◽  
Vol 89 (4) ◽  
pp. 844-851 ◽  
Author(s):  
Gilles Plourde ◽  
Chantal Villemure ◽  
Pierre Fiset ◽  
Vincent Bonhomme ◽  
Steven B. Backman

Background The auditory steady state response (ASSR) is a sustained electrical response of the brain to auditory stimuli delivered at fast rates (30-50 responses/s). The aim of this study was to evaluate the effect of 0.26-0.50% isoflurane on the ASSR and on consciousness, defined as responsiveness to verbal commands. Methods Ten volunteers (21-31 yr) participated. Isoflurane was administered at three stable, end-tidal concentrations: 0.26%, 0.38%, and 0.50%. The ASSR in response to 18,000 stimuli (500-Hz tonebursts, 10 ms, 82-dB, the right ear, 35-45 bursts/s) was recorded from the vertex with reference to the right mastoid. Recordings were made during baseline, at each isoflurane concentration, and during recovery. Results The mean (SD) ASSR amplitudes were 0.32 (0.23) microV during baseline, 0.24 (0.17) microV during 0.26% isoflurane, 0.09 (0.05) microV during 0.38% isoflurane, 0.04 (0.03) microV during 0.50% isoflurane, and 0.29 (0.33) microV during recovery. The amplitude during baseline and recovery was larger than during 0.38% and 0.50% isoflurane (P < 0.001). The amplitude at 0.26% was larger than at the other concentrations (P < 0.025). The logarithm of the ASSR amplitude was related linearly to the concentration of isoflurane (r = 0.85; P < 0.0001). The prediction probability (Pk) for loss of consciousness was 0.95 for both ASSR and measured isoflurane concentration. An ASSR amplitude < 0.07 microV was always associated with unconsciousness. Conclusions The ASSR is attenuated in a concentration-dependent manner by isoflurane. Suppression of consciousness and maximal attenuation of ASSR occur in the same isoflurane concentration range. Profound attenuation of ASSR appears to reflect unconsciousness, defined as unresponsiveness to verbal commands.


2002 ◽  
Vol 13 (05) ◽  
pp. 260-269 ◽  
Author(s):  
Barbara Cone-Wesson ◽  
John Parker ◽  
Nina Swiderski ◽  
Field Rickards

Two studies were aimed at developing the auditory steady-state response (ASSR) for universal newborn hearing screening. First, neonates who had passed auditory brainstem response, transient evoked otoacoustic emission, and distortion-product otoacoustic emission tests were also tested with ASSRs using modulated tones that varied in frequency and level. Pass rates were highest (> 90%) for amplitude-modulated tones presented at levels ≥ 69 dB SPL. The effect of modulation frequency on ASSR for 500- and 2000-Hz tones was evaluated in full-term and premature infants in the second study. Full-term infants had higher pass rates for 2000-Hz tones amplitude modulated at 74 to 106 Hz compared with pass rates for a 500-Hz tone modulated at 58 to 90 Hz. Premature infants had lower pass rates than full-term infants for both carrier frequencies. Systematic investigation of ASSR threshold and the effect of modulation frequency in neonates is needed to adapt the technique for screening.


2021 ◽  
Vol 11 (4) ◽  
pp. 1717
Author(s):  
Gilberto Gonzalez Avalos ◽  
Noe Barrera Gallegos ◽  
Gerardo Ayala-Jaimes ◽  
Aaron Padilla Garcia

The direct determination of the steady state response for linear time invariant (LTI) systems modeled by multibond graphs is presented. Firstly, a multiport junction structure of a multibond graph in an integral causality assignment (MBGI) to get the state space of the system is introduced. By assigning a derivative causality to the multiport storage elements, the multibond graph in a derivative causality (MBGD) is proposed. Based on this MBGD, a theorem to obtain the steady state response is presented. Two case studies to get the steady state of the state variables are applied. Both cases are modeled by multibond graphs, and the symbolic determination of the steady state is obtained. The simulation results using the 20-SIM software are numerically verified.


2020 ◽  
pp. 155005942098270
Author(s):  
Sarah Ahmed ◽  
Jennifer R. Lepock ◽  
Romina Mizrahi ◽  
R. Michael Bagby ◽  
Cory J. Gerritsen ◽  
...  

Aim Deficits in synchronous, gamma-frequency neural oscillations may contribute to schizophrenia patients’ real-world functional impairment and can be measured electroencephalographically using the auditory steady-state response (ASSR). Gamma ASSR deficits have been reported in schizophrenia patients and individuals at clinical high risk (CHR) for developing psychosis. We hypothesized that, in CHR patients, gamma ASSR would correlate with real-world functioning, consistent with a role for gamma synchrony deficits in functional impairment. Methods A total of 35 CHR patients rated on Global Functioning: Social and Role scales had EEG recorded while listening to 1-ms, 93-dB clicks presented at 40 Hz in 500-ms trains, in response to which 40-Hz evoked power and intertrial phase-locking factor (PLF) were measured. Results In CHR patients, lower 40-Hz PLF correlated with lower social functioning. Conclusions Gamma synchrony deficits may be a biomarker of real-world impairment at early stages of the schizophrenia disease trajectory.


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