[Pathogenesis of exercise induced asthma]. / Patogeneza astmy wysilkowej.

Exercise induced asthma is an exaggerated airway response to airway dehydration and the following mediators release from the inflammatory cells. The airway narrowing is primarily caused by bronchial smooth muscle contraction, but in milder form mucus production, airway edema and cough can be observed. In this study we have described some previously and currently proposed hypotheses which may explain pathomechanism of this form of bronchial hyperreactivity.

Effects of (-)-baclofen, clonazepam, and diazepam on tone exposure-induced hyperexcitability of the inferior colliculus in the rat: possible therapeutic implications for pharmacological management of tinnitus and hyperacusis.

Recent investigations in the authors' laboratory have shown that acute tone exposure (4 kHz continuous tone, 104 dB sound pressure level (SPL), 30-min duration) induces increases in the amplitude of click-evoked potentials in the inferior colliculus (IC). These increases have been attributed to a decrease in GABAA-mediated inhibition on IC neurons. In the present study, we examined the effects of three compounds (diazepam, clonazepam, and (-)-baclofen) that are known to enhance GABAergic inhibition on these tone exposure-induced increases and on changes in temporal integration in the IC. (-)-Baclofen was the only one of the three compounds tested that reversed in a dose-dependent manner the effects of tone exposure on both the amplitude of the click-evoked potentials recorded from the IC and on measures of the changes in temporal integration based on these potentials. Diazepam and clonazepam exhibited remarkably different effects on the click-evoked potentials recorded from the surface of the IC. Diazepam caused a dose-dependent decrease in one of the components of the IC potentials that reflects postsynaptic activity in the IC, whereas clonazepam caused a dose-dependent decrease in a peak that reflects input to the IC from the superior olivary complex (SOC). At dosages up to 40 mg/kg, neither diazepam nor clonazepam reversed the changes in temporal integration in the IC that were induced by the tone exposure; diazepam caused a small, but statistically significant, enhancement of the effects of tone exposure on this function. The results of this study show that (-)-baclofen is a potent modulator of both the excitability of neurons in the ascending auditory pathway and the processing of auditory information by IC neurons. The finding of the present study that two benzodiazepines (clonazepam and diazepam) have remarkably different effects on evoked potentials, which reflects both input to the IC and postsynaptic events in the IC neurons, suggests heterogenicity of the GABAA receptor from one structure to another in the ascending auditory pathway. We suggest that (-)-baclofen may be clinically useful in treating disorders of the auditory system that are caused by plasticity in the ascending auditory pathway.

Evidence of neuronal plasticity within the inferior colliculus after noise exposure: a study of evoked potentials in the rat.

Recent investigations have implicated that the central nervous system has a role in the changes that occur in auditory function following acoustic trauma caused by noise exposure. These investigations indicate that the inferior colliculus may be the primary anatomical location in the ascending auditory pathway where noise-induced neuronal plasticity occurs, thereby resulting in changes in the neuronal processing of auditory information. In the present investigation, we show that the amplitudes of all peaks in the click-evoked response from the external nucleus of the inferior colliculus decrease during a 30 min exposure to a tone (104 dB sound pressure level (SPL) at 4 kHz and 8 kHz). After tone exposure, the amplitudes of two of the peaks of the response from the external nucleus of the inferior colliculus that reflect the input from more caudal structures slowly returned to baseline levels, whereas the amplitudes of the two peaks reflecting neuronal activity in the inferior colliculus increased above baseline levels and remained at the increased levels for at least 90 min following exposure to the tone. We also show that exposure to a 4 kHz tone at 104 dB SPL causes changes in the neuronal processing of tonebursts in the form of changes in the temporal integration function for one of the peaks of the response from the external nucleus of the inferior colliculus that originates in the inferior colliculus. Before tone exposure the amplitude of this peak decreased with increasing stimulus duration, but after tone exposure the amplitude of this peak was independent of the duration of the toneburst stimulus. We interpret these changes as evidence that noise exposure (tone exposure) causes changes in the excitability of the inferior colliculus that are not seen in more caudal structures, and these changes are probably a result of a change in the balance between inhibition and excitation in the inferior colliculus.

Evidence of decreased GABAergic influence on temporal integration in the inferior colliculus following acute noise exposure: a study of evoked potentials in the rat.

Many investigations have shown that modulation of sensory input, either by over stimulation or sensory deprivation, can cause a reorganization of structures located high in the central nervous system (CNS). Although most of these studies had focused on studying changes in the function and tonotopic organization of the sensory cortex, recent evidence has suggested that plastic changes in specific subcortical nuclei of sensory systems may also occur in response to modulation of sensory input, and may be partially responsible for changes reflected at the level of the cortex. In the present study we investigated the effects of noise exposure (4-kHz continuous tone at 104 dB sound pressure level (SPL) for 30 min duration) on the processing of auditory information at the level of the inferior colliculus (IC). We studied how evoked potentials recorded from the surface of the IC changed as a function of the duration of the tone bursts used as stimuli. We measured the amplitude of a peak that is generated postsynaptically in the IC in response to tone bursts between 1 and 6 ms duration. In animals that were not exposed to the tone, the amplitude of this peak decreased with increasing stimulus duration, but after tone exposure, the decrease in the amplitude of this peak was significantly less than in the animals not exposed to the tone. A microinjection of the GABAA antagonist, bicucullene, into the IC in the animals not exposed to the tone caused the amplitude of the peak to be less dependent on tone burst duration, which indicates that the decrease in the amplitude of this component of the response from the IC with increasing stimulus duration is a result of GABAA mediated inhibition on IC neurons. The tone exposure caused a similar decrease in amplitude of this component of the response from the IC, thus indicating that noise exposure reduced the GABAA mediated component of this function. This is supported by the finding that microinjections of bicucullene into the IC of noise-exposed animals did not significantly change the relationship between the amplitude of this peak and the stimulus duration.

Effects of L-baclofen and D-baclofen on the auditory system: a study of click-evoked potentials from the inferior colliculus in the rat.

The drug baclofen is a potential treatment for severe tinnitus, but its action in relieving tinnitus is not known. Baclofen is available as an approved drug only in racemic form with about equal content of the two enantiomers. In the present paper we show that L-baclofen causes a considerable (40.7%) suppression of the amplitude of the second peak in the click-evoked response from the cochlear nucleus. Bipolar recordings from the external nucleus of the inferior colliculus showed that L-baclofen caused a reduction in the amplitude of three or four distinct peaks in this response. D-Baclofen had no detectable effect on the response from the cochlear nucleus, and had only a slight effect on one component of the response from the external nucleus of the inferior colliculus. The demonstrated effect of L-baclofen on excitation in the ascending auditory pathway indicates that this drug may be a potential treatment for hyperactive auditory disorders such as tinnitus and hyperacusis.

Liquid state membrane electrode sensitive to Ln(III).

A liquid ion-exchange electrode containing a chloroform solution of the complex of Ln(III) (Gd, La) with tetraphenyl ester of imidodiphosphoric acid is described. The slope of the calibration graph (electrode potential vs concentration) is 18.5 mV/pLn in the pLn range 4.7-2 (pH = 5). Fe(III), Al(III), Co(II), Ni(II) and Ca(II) ions do not interfere, unlike ions of other lanthanides. It was found that the electrode might be applied to detect the end point of the titration of Ln(3+) ions.

Interaction between auditory and somatosensory systems: a study of evoked potentials in the inferior colliculus.

It is known that some neurons in the external nucleus of the inferior colliculus (ICX) receive both auditory and somatosensory input. In recordings of evoked potentials from the ICX in the rat we show evidence that somatosensory activation can modify the auditory response to click stimulation. Electrical stimulation of the median nerve affects the click-evoked response that is recorded from the surface of the ICX and different components of the response were affected differently. The magnitude of the changes was dependent on the time interval between electrical stimulation of the median nerve and presentation of the click stimulation. The amplitude of the two earliest peaks in the click-evoked ICX response increased slightly (16% and 20%, respectively; average of recordings in 10 animals) as a result of stimulation of the median nerve, while the amplitudes of two later peaks decreased as a result of stimulation of the median nerve (the average decrease in amplitude of these two peaks in recordings in 10 animals was 18 and 26%, respectively). The latencies of the 3 peaks we studied were only slightly affected, and the maximal change was 0.07 and 0.25 msec, respectively, for the 2 earliest peaks. The decrease in the amplitude of specific peaks of the ICX response confirms that some neurons of the extralemniscal system receive both auditory and somatosensory input, and that such somatosensory input is mainly inhibitory on these neurons. We interpret the increase in the amplitude of the early peak to be a result of median nerve stimulation caused by a decreased centrifugal inhibitory influence on superior olivary neurons.

Spectrophotometric determination of ketotifen in pharmaceutical preparations after isolation on ion-exchanger.

Spectrophotometric method have been proposed for the determination of ketotifen in complex "Position" (Polfa-Poznan) samples after preliminary separation of excipients. For the determinations of the ketotifen in Pozitan a relative standard deviation of +/-2.0% was found.

Use of a bismuth ion-selective electrode for investigation of bismuth complexes of citric and malic acids.

A bismuth ion-selective electrode has been used to determine the nature and stability of the complexes formed by bismuth with citric acid and malic acid, by measurement of the response of the electrode to different total bismuth concentrations at various combinations of pH and total ligand concentration. The values found were beta(2) = 3 x 10(13) for Bi(Cit)(2)(3-) and beta(3) = 8 x 10(9) for Bi(Mal)(2)(3-).

Determination of bismuth(III) by direct potentiometry and potentiometric titration, with an electrode sensitive to Bi(3+).

A liquid-state ion-exchange electrode containing the chelate bismuth(III) complex with 5-mercapto-3-(naphthyl-2)-1,3,4-thiadiazole-2-thione in tetrachloroethane is applied to the determination of bismuth(III) by direct potentiometry and potentiometric titration. The influence of various interfering cations is discussed. In the presence of potassium cyanide as masking agent, Ni(II), Co(II), Cu(II), Ag(I) and Hg(II) do not interfere in the potentiometric EDTA titration. Satisfactory results have been obtained for the determination of bismuth(III) in Wood's metal and two pharmaceuticals.

Liquid-state membrane electrode sensitive to bismuth(III).

A liquid ion-exchange electrode containing a tetrachloraethane solution of the complex of bismuth(III) with 5-mercapto-3-(naphthyl-1)-1,3,4-thiadiazol-2-thione is described. The electrode is sensitive to Bi(3+). The slope of the calibration graph (electrode potential vs. concentration) is 18.7 mV pBi in the pBi range 6.5-9.5 in ammonium acetate buffer (pH = 4.0). Bivalent cations and Al(III), Fe(III) and Th(IV) do not interfere (K(Bi(3+)+,(M(2+)))<10(-5)). The dissociation constant of bismuth acetate has been determined with the aid of the electrode.