Endolymphatic leakage in case of acute loss of cochlear microphonics

Summary Rapid loss of cochlear microphonics in guinea-pigs previously exposed to high-energy impulse noise was shown to be related to the breakdown of the endolymphatic boundary. The cochlear duct was rendered leaky by deterioration of the reticular membrane, and damage of sensory and supporting cells.Aided by grants from the Ministerium für Gesundheitswesen der DDR.     

Der Einfluss der Reizbedingungen auf den initialen Abfall der Cochlearpotentiale bei totaler Ischämie

Summary The rapid initial drop of the cochlear microphonic potential following compression of the aorta was studied in guinea pigs. The intensity of the stimulus, either continuous or intermittent, was without influence on the half-time of amplitude (t/2=52±7 s;n=18). From this it is concluded that the metabolism of the generator responsible for the cochlear microphonic is unaffected by the type or intensity of stimulation. The lower resistance of the neural action potential to ischemia was confirmed (t/2=18±2 s;n=5).     

Effects of increased potassium in scala tympani on auditory nerve sensitivity.

Raising the K+ concentration in scala tympani of the guinea-pig cochlea generally caused a substantial increase in the spontaneous firing rate of single auditory nerve fibres. This effect was not accompanied by any observed reduction in the threshold sensitivity of these fibres. These findings cast doubt on current theories of cochlear transduction.     

Effects of increased potassium in scala tympani on auditory nerve sensitivity

Summary Raising the K⁺ concentration in scala tympani of the guinea-pig cochlea generally caused a substantial increase in the spontaneous firing rate of single auditory nerve fibres. This effect was not accompanied by any observed reduction in the threshold sensitivity of these fibres. These findings cast doubt on current theories of cochlear transduction.G. Leng was supported by the S.R.C.     

Sound-stimulated14C-glutamate release from the nucleus cochlearis

Summary The exogenous release of glutamate has been successfully studied in the cochlear nucleus of guinea-pigs after physiological sound stimulation of the ear (frequency 2000–20,000 Hz at 100 dBA).Acknowledgments. This study was supported by grants from the Swedish Medical Research Council (B80-12X-05666-01) and Torsten Söderbergs och Ragnar Söderbergs stiftelser.     

De l'opportunité de quelques équations différentielles en vestibulométrie

Summary On the basis of wide experience in electronystagmography, the author has attempted to establish a characteristic and general relationship between the cupulo-ampullary system of the labyrinth underlining the mathematical parallelism with the cochlear system. At the same time, some partial physico-mathematical analogies, which were expressed concerning the same subject, are criticized.     

siRNA-mediated knock-down of NOX3: therapy for hearing loss?

Cisplatin is a widely used chemotherapeutic agent that causes significant hearing loss. Previous studies have shown that cisplatin exposure is associated with increase in reactive oxygen species (ROS) in the cochlea. The inner ear expresses a unique isoform of NADPH oxidase, NOX3. This enzyme may be the primary source of ROS generation in the cochlea. The knockdown of NOX3 by pretreatment with siRNA prevented cisplatin ototoxicity, as demonstrated by preservation of hearing thresholds and inner ear sensory cells. Trans-tympanic NOX3 siRNA reduced the expression of NOX3 and biomarkers of cochlear damage, including transient receptor vanilloid 1 (TRPV1) channel and kidney injury molecule-1 (KIM-1) in cochlear tissues. In addition, siRNA against NOX3 reduced apoptosis as demonstrated by TUNEL staining, and prevented the increased expression of Bax and abrogated the decrease in Bcl2 expression following cisplatin administration. Trans-tympanic administration of siRNA directed against NOX3 may provide a useful method of attenuating cisplatin ototoxicity. In this paper, we review recent publications dealing with the role of NOX3 in ototoxicity and the effects of siRNA against cisplatin-induced hearing loss.     

Differential distribution of TASK-1, TASK-2 and TASK-3 immunoreactivities in the rat and human cerebellum

In this work, the distributions of some acid-sensitive two-pore-domain K⁺ channels (TASK-1, TASK-2 and TASK-3) were investigated in the rat and human cerebellum. Astrocytes situated in rat cerebellar tissue sections were positive for TASK-2 channels. Purkinje cells were strongly stained and granule cells and astrocytes were moderately positive for TASK-3. Astrocytes isolated from the hippocampus, cerebellum and cochlear nucleus expressed TASK channels in a primary tissue culture. Our results suggest that TASK channel expression may be significant in the endoplasmic reticulum of the astrocytes. The human cerebellum showed weak TASK-2 immunolabelling. The pia mater, astrocytes, Purkinje and granule cells demonstrated strong TASK-1 and TASK-3 positivities. The TASK-3 labelling was stronger in general, but it was particularly intense in the Purkinje cells and pia mater.Received 25 February 2004; received after revision 19 April 2004; accepted 28 April 2004     

Hearing molecules: contributions from genetic deafness

Considerable progress has been made over the past decade identifying many genes associated with deafness. With the identification of these hereditary deafness genes and the proteins they encode, molecular elements of basic hearing mechanisms emerge. As functional studies of these molecular elements become available, we can put together the pieces of the puzzle and begin to reach an understanding of the molecular mechanisms of hearing. The goal of this review is to discuss studies over the past decade that address the function of the proteins implicated in genetic deafness and to place them in the context of basic molecular mechanisms in hearing. The first part of this review highlights structural and functional features of the cochlea and auditory nerve. This background will provide a context for the second part, which addresses the molecular mechanisms underlying cochlear function as elucidated by genetic causes of deafness. Received 20 September 2006; received after revision 24 October 2006; accepted 5 December 2006     

HCN channels contribute to the intrinsic activity of cochlear pyramidal cells

A hyperpolarization-activated current recorded from the pyramidal cells of the dorsal cochlear nucleus was investigated in the present study by using 150- to 200-m-thick brain slices prepared from 6- to 14-day-old Wistar rats. The pyramidal neurones exhibited a slowly activating inward current on hyperpolarization. The reversal potential of this component was –32 ± 3 mV (mean ± SE, n = 6), while its half-activation voltage was –99 ± 1 mV with a slope factor of 10.9 ± 0.4 mV (n = 27). This current was highly sensitive to the extracellular application of both 1 mM Cs⁺ and 10 M ZD7288. The electrophysiological properties and the pharmacological sensitivity of this current indicated that it corresponded to a hyperpolarization-activated non-specific cationic current (I_h). Our experiments showed that there was a correlation between the availability of the h-current and the spontaneous activity of the pyramidal cells, suggesting that this conductance acts as a pacemaker current in these neurones. Immunocytochemical experiments were also conducted on freshly isolated pyramidal cells to demonstrate the possible subunit composition of the channels responsible for the genesis of the pyramidal h-current. These investigations indicated the presence of HCN1, HCN2 and HCN4 subunits in the pyramidal cells.Received 15 May 2003; received after revision 26 June 2003; accepted 21 July 2003     

Die Reizschwelle der Sinnesorgane als physikalisches Problem

Summary A survey is given of recent work on physical aspects of sensory processes. The reasoning which leads to the generally recognized view that one rod of the retina is excited by only one quantum of light is given in par. II. In par. IIIa summary is given of the papers byHecht andVan der Velden on the number of rods which must be struck in order to obtaina sensation of light. Par. III describes the role of the quantum character of light at higher intensities (de Vries), where it sets a limit to intensity discrimination and visual acuity. The influence of Brownian movement on the process of hearing is discussed in par. VI. It is found that the Brownian movement of the inner ear is close to the threshold actually observed (de Vries), whereas the Brownian motion of the air at the eardrum (seeSivian andWhite) is below the audible threshold. The role of the Brownian movementin the sense cells is described in par. VII; the results are used for an analysis of the mechanism of hearing (see alsode Vries); evidence is obtained that electric voltages are generated in the tectorial membrane (the well-known cochlear microphonics) and that they play an important part in the mechanism of energy transfer to the sense cells (similar voltages were also derived from the cupolæ in the lateral lines of fishes by the present author). Finally some physical arguments are sumarized againstYeagley's theory of bird navigation.     

Biodegradation of nitrilotriacetic acid (NTA) in the absence of oxygen

Summary A microbiol culture able to grow in the absence of oxygen with nitrilotriacetate (NTA) as the sole source of carbon and energy was enriched from river sediment. Growth was strictly dependent on the presence of nitrate and the results indicate that nitrate was exclusively used as the electron acceptor and was reduced to dinitrogen (N₂). The stoichiometry of anaerobic NTA degradation by the enrichment culture was determined.     

Lymphatic metastasis of tumour; persistent transport of cells

Summary A model of lymphatic metastasis established by injecting Walker rat carcinoma cells into the rat footpad was used to study the output of tumour cells from the footpad. The lymphatic efferent from the footpad was cannulated in a group of rats with advanced neoplasm; it was shown that the output of tumou cells was continuou over periods up to 90 min and ranged from 10²–10⁵ cells/min.Acknowledgment. This work was supported by a grant from the National Cancer Institute of Canada to C.R.F. and I.C. We are grateful to Mrs W. Kao and Mr I. Etches for meticulous technical help and to the Photographic Section, Department of Pathology for illustrations. Dr V.S. Gupta of Veterinary Physiology, University of Saskatchewan supplied the tumour for transplantation.     

Y型明渠交汇水流分离区的数值分析

针对Y型明渠交汇口的水流特性，应用三维各向异性的雷诺应力模型，采用交错网格上的有限体积法离散控制方程，用SIMPLE算法求解压力-速度场。数值计算结果与物理模型试验结果吻合较好，并据此重点探讨了不同交汇角条件下交汇口分离区尺寸的变化规律，提出Y型交汇水流分离区的定义和分离区尺寸与汇流比的函数关系。     

Quantitative determination of the activity of acid peptidases of industrial origin]

Reagent ninhydrine-Cd++, reacts with free alpha and epsilon amino groups of proteins. Horse-heart apomyoglobin was subjected to exhaustive succinylation, rendering the product non reactive to ninhydrine. The succinylglobin was submitted to enzyme digestion at pH 2.0, 4.0, 4.7 and 6.0. The commercially available enzymes contain mainly pepsin-like and chymosin-like enzymes. The enzymatic digests of succinyl-globin contain new free alpha-amino groups reacting with ninhydrin. Enzymatic digestion was performed under various condition (ratio E/S, pH). The results were compared to those obtained with synthetic substrate: PRO-HIS-LEU-SER-PHE(NO2)-NLEU-ALA-LEU-OME. The price of the synthetic substrate used, was more than 100 times the cost of succinyl-globin, thus the use of this substrate is a valuable tool for the quantitative estimation of peptidase activity in commercially available (pepsin, chymosin-like) enzymes.     

Lymphatic metastasis of tumour; persistent transport of cells.

A model of lymphatic metastasis established by injecting Walker rat carcinoma cells into the rat footpad was used to study the output of tumour cells from the footpad. The lymphatic efferent from the footpad was cannulated in a group of rats with advanced neoplasm; it was shown that the output of tumour cells was continuous over periods up to 90 min and ranged from 10(2)-10(5) cells/min.     

Inhibition of collagen synthesis by interleukin-1 in three-dimensional collagen lattice cultures of fibroblasts

Interleukin-1 (Il-1) was added to collagen lattice cultures of human skin fibroblasts. No cell division was induced, the ability of fibroblasts to contract the lattices was decreased and a dose-related inhibition of collagen synthesis without effect on non-collagen proteins was found. Indomethacin had no influence on these effects.     

Stimulation of proliferation of rat spleen cells, in vitro, by a nonspecific acute inflammatory exudate. Modulation of cell response to phytohemagglutinin (PHA)]

The effect of an acute non-specific inflammatory exudate with mitogenic activity on macrophages in culture has been tested on the spontaneous and PHA-induced DNA synthesis of spleen cells in vitro. Stimulatory effect of this exudate was observed on spontaneous DNA synthesis which was detectable over a range of 1 : 4 to 1 : 4,000 concentrations. After optimal PHA stimulation, an inhibition of mitogen-induced DNA synthesis was observed when the cells were exposed to the highest concentrations (up to 1 : 128) of the exudate. Thereafter, the phenomenon could be reversed and the stimulation was maximal at a concentration of 1 : 2,000. When a sub-optimal dose of PHA was used, the simulatory effect was more pronounced and detected from 1 : 8 up to 1 : 4,000 concentrations.     

Further characterization of the effects of ultraviolet irradiation of the amphibian egg

UV-irradiation of the vegetal hemisphere of amphibian eggs leads to developmental abnormalities in neural morphogenesis. The possibility that the egg's transient sensitivity to irradiation could be due to pigmentation changes was examined in albino eggs. The tissue specificity of the effects of irradiation was analyzed by exchanging the ectoderm between irradiated and control embryos.     

Inhibition of collagen synthesis by interleukin-1 in three-dimensional collagen lattice cultures of fibroblasts

Summary Interleukin-1 (II-1) was added to collagen lattice cultures of human skin fibroblasts. No cell division was induced, the ability of fibroblasts to contract the lattices was decreased and a dose-related inhibition of collagen synthesis without effect on non-collagen proteins was found. Indomethacin had no influence on these effects.