The effect of caffeic acid phenethyl ester on the prevention of experimentally induced myringosclerosis

OBJECTIVES: Myringosclerosis is a common sequela of ventilation tube insertion for the treatment of the otitis media with effusion. Several antioxidants have been identified to prevent myringosclerosis. The objective of this study was to investigate the effect of caffeic acid phenethyl ester (CAPE) on the prevention of experimentally induced myringosclerosis. METHODS: Thirty-five Sprague-Dawley rats were unilaterally myringotomized. The rats were divided into four groups randomly: group 1 received no treatment, group 2 received intraperitoneally administered saline and group 3 received intraperitoneally administered CAPE. The tympanic membranes were examined by otomicroscopy on the 15th day after treatment. The membranes were then harvested and evaluated histologically by light microscopy. RESULTS: The tympanic membranes from group 1 showed extensive myringosclerosis; those from group 2 showed a similar occurrence of myringosclerosis. However, group 3 had a reduced occurrence of myringosclerosis by otomicroscopic evaluation. Under light microscopic examination, the lamina propria of the pars tensa was found to be thicker and more sclerotic in groups 1 and 2 when compared with group 3. CONCLUSIONS: Systemic treatment with CAPE was found to be effective in the prevention of sclerotic lesions in myringotomized rat tympanic membranes.     

A study of efficacy of Nigella sativa in treatment of Meniere's disease: A randomized,placebo controlled clinical trial

PurposeMeniere's disease (MD), first introduced by Prosper Meniere, is characterized mainly by vertigo, tinnitus, aural fullness and sensorineural hearing loss. Though the exact pathophysiology of MD is unknown, immunologic and inflammatory interactions are possible underlying mechanisms involved in MD. This study is aimed to investigate the immunomodulatory and anti-inflammatory effect of Nigella sativa on MD as a therapeutic agent.MethodsWe divided 40 patients with definite MD into two groups of 20 cases. The study group received 1 g of Nigella sativa oil daily for three months and the control group received a placebo. Changes in hearing, tinnitus and vertigo were estimated by pure tone audiometry, tinnitus handicap inventory questionnaire and dizziness handicap inventory questionnaire, respectively.ResultsAt the end of the study we did not observe any significant improvement in study's group hearing threshold, tinnitus and vertigo compared to the control group.ConclusionsIn this study, statistical analysis showed that Nigella sativa failed to improve signs and symptoms of MD. However, further investigations with a larger study population are needed to ascertain the current conclusion.     

高速率电刺激对豚鼠听神经兴奋性的影响

目的：评估高速率电刺激对豚鼠听神经兴奋性的影响。方法：切开受试豚鼠圆窗膜,标准电极插入鼓阶大约4mm,两个靠近蜗尖的电极作为刺激电极,切开圆窗用压碎的颞肌封住。随机选择一耳为刺激耳,另一耳则为对照耳,均安装上标准电极,刺激电极在整个测试过程中保持不动。在保持刺激强度处在临床正常水平[电刺激诱发听觉脑干电位(EABR)阈值上6dB]情况下,用200(n=14)、400(n=10)、1000(n=11)、2000(n=10)脉冲数／s(PPS)四种不同的电刺激速率急性刺激45只听力正常豚鼠鼓阶内电极2h,记录急性刺激前、后3h内EABR的阈值和Ⅰ波幅值,比较急性刺激前、后EABR的Ⅰ波幅值的变化。结果：急性刺激电流强度固定在临床正常水平(EABR阈上6dB),急性刺激后EABR的Ⅰ波幅值同急性刺激前相比,采用200PPS刺激速率平均约升高20％;400PPS约升高9％;1000PPS约升高7％;2000PPS约升高30％。结论：在刺激电流强度为阈上6dB的情况下,人工耳蜗言语编码策略如果应用1000、2000PPS高速率电刺激不会导致听神经的兴奋性下降。此实验为临床上研制新的人工耳蜗采取高刺激速率语音信号处理方案提供了依据。     

The preventive effect of N-nitro L-arginine methyl ester in experimentally induced myringosclerosis

Objective

The purpose of this study was to investigate the antiinflammatory and antifibrotic effects of N-nitro l-arginine methyl ester (l-NAME) in experimentally induced myringosclerosis.

Methods

Twenty Wistar albino rats were bilaterally myringotomized and divided randomly into four groups, each including five rats. Group I received no treatment, Group II was treated with topical saline solution, Group III received topical l-NAME and Group IV received intraperitoneally administered l-NAME. After 2 weeks, the tympanic membranes were examined and scored by otomicroscopy regarding the extent of the myringosclerosis. Then the tympanic membranes were harvested and evaluated histopathologically by light microscopy. The intensity of inflammation and degree of myringosclerosis were evaluated, the mean thickness of tympanic membranes were also measured.

Results

The tympanic membranes of Groups I and II showed extensive myringosclerosis in contrast to those of Groups III and IV which had significantly less or no changes (p < 0.05). The inflammation and fibroblastic activity of the lamina propria in the tympanic membranes of Groups III and IV were found to be significantly less pronounced (p < 0.05). The tympanic membranes were found to be significantly thicker in Groups I and II when compared with Groups III and IV (p < 0.05).

Conclusion

Our results showed that both topical and intraperitoneal applications of l-NAME supressed inflammation, reduced fibroblastic proliferation and decreased the formation of myringosclerosis in myringotomized rat tympanic membranes.     

葛根对老年豚鼠听功能的保护作用

目的 观察葛根是否对老年豚鼠听功能具有保护作用.方法 选取16只28～30月龄豚鼠,随机分为用药组和对照组,每组8只.用药组豚鼠皮下注射葛根提取液2 g·kg~(-1)·d~(-1),对照组使用等量生理盐水注射,共8周.观察两组豚鼠用药前及用药结束后ABR反应阈的变化;应用基底膜荧光染色铺片比较两组动物基底膜的变化.结果 注射葛根后用药组ABR反应阈提高4.84±3.28 dB,较对照组(11.12±3.72 dB)明显减少(P<0.05),基底膜荧光染色铺片显示用药组毛细胞缺失数目较对照组减少.结论 葛根对老年豚鼠听功能具有保护作用.     

间隔标记信号带宽和强度对豚鼠下丘间隔反应的影响

目的探讨间隔检测中间隔标记信号的带宽和强度对豚鼠下丘间隔反应阈值的影响。方法经豚鼠下丘埋植金属电极，记录4种带宽间隔标记信号和3个强度下的间隔反应，得出间隔阈值。结果与以往行为实验结果类似，相同声音强度下，豚鼠下丘的间隔反应阈值随着间隔标记信号带宽的增加而下降。例如在85dBSPL时，0．5～8kHz，0．5～16kHz及0．5～32kHz带宽下的间隔反应阈值分别为1．35±0．32ms，1．33±0．33ms及1．17±0．44ms。但是在最高频段（16～32kHz）和线性等带宽低频段（0．5～16kHz），间隔反应阈值未见显著差异，提示高频段的时间分辨可能与低频段相当。相同间隔标记带宽下，声音强度愈低，间隔反应阈值愈大；但仅在最低频段（0．5～8kHz）声音强度效应具有显著性意义。结论豚鼠下丘的间隔反应阈值主要决定于间隔标记信号的总带宽而非频带位置；信号强度也对该阈值有一定影响。     

缝隙连接阻断剂1-庚醇对豚鼠听觉的作用

目的：探讨缝隙连接在维持正常的听功能方面可能发挥的作用。方法：通过向豚鼠外淋巴中注入缝隙连接阻断剂1-庚醇（1-heptanol），然后检测给药前后豚鼠听性脑干诱发反应（ABR）阈值和潜伏期的改变，并借助透射电镜观察药物对豚鼠耳蜗中的缝隙连接结构的影响。结果：注射1-heptanol后，豚鼠ABR阈值显著提高，潜伏期延长（P〈0．01），并随时间推移呈动态升高趋势。同时，通过电镜可以观察到在豚鼠耳蜗中存在着大量的缝隙连接结构，其主要分布在毛细胞和其下的支持细胞间。1-heptanol可以使缝隙连接结构破坏，毛细胞水肿、变性。结论：缝隙连接阻断剂1-heptanol能明显影响豚鼠的听功能，缝隙连接结构在听觉形成过程中起着重要的作用。     

The effect of cidofovir on cytomegalovirus-induced hearing loss in a Guinea pig model

OBJECTIVE: To evaluate the utility of therapy with the cyclic cogener of the anti-cytomegalovirus (CMV) agent cidofovir against CMV-induced hearing loss in a guinea pig model. DESIGN: Thirty-six guinea pigs were randomly divided into 4 groups of 9. All groups underwent auditory brainstem response testing on days 0, 4, 7, 14, 21, and 28. Group 1 received no intervention. Group 2 underwent sham surgery consisting of unilateral round window injection of 25 microL of sterile viral media on day 0. Groups 3 and 4 underwent round window injection of 1.7 x 10(5) plaque-forming units of guinea pig CMV on day 0. Group 4 received antiviral treatment with intraperitoneal injection of cidofovir (20 mg/kg) on days 1 and 5 after inoculation. SETTING: An animal research facility. SUBJECTS: Thirty-six weanling Hartley guinea pigs. RESULTS: Of the animals who received guinea pig CMV and no cidofovir treatment, 4 of 9 (day 4) and 5 of 9 (days 7 and 28) demonstrated a hearing loss of at least 30 dB. In contrast, none of the animals in the untreated, sham surgery, or cidofovir-treated groups had a hearing loss of greater than 20 dB. This difference was statistically significant for day 4 (P = .04, 1-tailed Fisher exact test), day 7 (P = .01), and day 28 (P = .01). Histologic evaluation of hearing-impaired animals revealed inflammatory infiltrates, particularly in the scala tympani. Fibrosis of the basal turn of the cochlea was observed in 7 of 9 untreated animals and 1 of 9 treated animals. CONCLUSION: Cidofovir therapy prevents CMV-induced hearing loss and associated histologic changes in guinea pigs.     

外淋巴“枯竭“状态对听神经兴奋性影响

目的 通过记录电刺激诱发听觉脑干电位(EABR)阈值变化搞清楚内耳外淋巴“枯竭”状态对听神经兴奋性影响。方法 在手术显微镜帮助下,小心把标准刺激电极沿蜗轴插入鼓阶约4mm,用压碎的肌肉轻轻封住圆窗口。然后用波宽为50μs/phase、刺激速率为30次/秒电荷平衡双相脉冲电流刺激受试动物鼓阶内的靠近蜗尖的电极对(1/2),记录两次EABR阈值,取均值。然后把明胶海绵做成直径约为1mm,长约为4cm小的圆柱形,把一端放入前庭阶持续吸干外淋巴,直到显微镜下见鼓阶外淋巴消失,模拟外淋巴“枯竭”状,用以上电刺激参数再次记录电极对(1/2)的EABR阈值两次,取均值。比较前后两次EABR阈值的变化(t检验)。结果 耳蜗外淋巴“枯竭”状态时测试到的EABABR阈值0.63±0.11mA较充满外淋巴时0.27±0.08mA明显升高(P<0.001)。结论 EABR阈值升高说明耳蜗鼓阶外淋巴呈现“枯竭”状态时听神经兴奋性明显下降,临床上少数重聋或者全聋患者耳蜗外淋巴呈现“枯竭”状态,推测其电子耳蜗植入临床效果可能较耳蜗鼓阶内外淋巴正常患者差。     

氨基苷类药物对内淋巴积水豚鼠前庭及耳蜗功能的影响

目的探讨氨基甙类药物对内淋巴积水豚鼠前庭及耳蜗功能的影响。方法8只内淋巴积水模型豚鼠全身应用链霉素,观察给药前后豚鼠行为学、眼震电图(ENG),听性脑干反应(ABR),畸变产物耳声发射(DPOAE)及形态学变化。结果给药后未出现头偏斜、走路不稳等前庭功能紊乱的行为征象,连续给药第10天、停药后第7天摆动幅度90°,停药后第21天,摆动幅度为90°、120°时积水侧眼震反应降低的幅度明显大于对照耳(     

Effects of anoxia on the cochlear summating potential in the guinea pig

Summary The cochlear summating potential (SP) was recorded extracochlearly from the apex and the round window in 25 guinea pigs, applying anoxia during periods of 1–2 min. For 2 and 8 kHz tone pips at 80 and 60 dB SPL, respectively, the initially negative SP at the apex diminished and even became positive during oxygen cut-off. After restoration of oxygenation, the change in SP reversed direction and was followed by a large negative undershoot. At the round window, the initially positive SP evoked by 8 kHz, 60 dB SPL tone pips followed exactly the same time course, but with inverted polarity, while the majority of the recordings of the initially negative SP evoked by 2 kHz, 80 dB SPL tone pips followed a course similar to the apical negative SP. However, the negative round window SP showed only slight polarity reversal and no undershoot. A small number of the recordings at the round window for 2 kHz showed an increase of the negative SP during anoxia followed by a decline of the SP and recovery after anoxia. The similar time course of the initially negative SP at the apex and the initially positive SP at the round window failed to support the hypothesis of a multi-component SP. However, the polarity reversal during anoxia and the different reactions to anoxia of the 2 kHz round-window SP suggest that the SP may consist of several different components.     

豚鼠鼓室导抗图正常值测试及结果分析

目的研究豚鼠鼓室导抗图（tympanogram）各个测试项目的正常值范围及不同性别、耳别之间的差异。方法选取ABR反应阈正常、无耳科疾病的正常豚鼠40只,在麻醉状态下测试其鼓室导抗图,并对不同性别、耳别的各个测试项目的结果进行比较。结果所有鼓室导抗图均符合Jerger分类法中的“A”型曲线,其等效外耳道容积约为0．09&#177;0．02ml,静态声顺值约为0．10&#177;0．03ml,坡度约为0．14&#177;0．06ml,峰压值约为一99．44&#177;75．06daPa。等效外耳道容积在性别间的差异具有统计学意义（P=0．012）,而静态声顺值、坡度和峰压值差异均无统计学意义（P〉0．05）。左右耳间各指标差异均无统计学意义（P〉0．05）。结论雄性与雌性豚鼠鼓室导抗图的等效外耳道容积存在显著性差异,其他各指标的结果在不同性别、耳别之间无明显差异。     

The effect of L-carnitine on the prevention of experimentally induced myringosclerosis in rats

The objective of this study was to investigate the possible effect of L-carnitine on the prevention of experimentally induced myringosclerosis. Twenty Sprague-Dawley rats were bilaterally myringotomized. The rats were divided into two groups randomly: group 1 which were intraperitoneally administered saline and group 2 which were intraperitoneally administered L-carnitine. Blood samples were collected for biochemical evaluation and the tympanic membranes were harvested after 28 days. Histopathological and immunohistochemical evaluation were done under light microscopy. The mean malondialdehyde levels were 3.9+/-0.9 in group 2, and 7.9+/-1.1 in group 1 (P<0.001), nitric oxide levels were 25.6+/-6.4 in group 2 and 30.8+/-8.2 in group 1 (P=0.14) and acetylcholinesterase was 1035+/-60 in group 2 and 678+/-35 in group 1 (P=0.001). Myringosclerosis was more frequent and severe in group 1 than group 2 (P<0.007). Immunoreactivity was seen in 16 of 20 tympanic membranes in group 2 and six of 20 tympanic membranes in group 1 (P=0.005). We conclude that L-carnitine diminishes the occurrence of myringosclerosis in rats after myringotomy possibly by antioxidant activity and decreasing the formation of reactive oxygen species.     

豚鼠畸变产物耳声发射的检测

目的 :建立稳定可靠的检测动物畸变产物耳声发射的方法。方法 :采用预先手术切除耳屏软骨 ,加用自制探头套管 ,选择复合麻醉等改良方法 ,测量健康杂色豚鼠 7只 ( 13耳 ) 2、4、6k Hz畸变产物耳声发射( DPOAE)输入输出 ( I/ O )曲线、潜伏期等指标。结果 :各频率 DPOAE引出率均为 10 0 % ,I/ O曲线最大幅值分别为 ( 2 7.2 4± 4 .15 ) d B SPL ,( 2 7.98± 4 .0 5 ) d B SPL和 ( 4 1.4 5± 1.2 0 ) d B SPL ;潜伏期为 ( 2 .0 6± 0 .2 1) m s,( 1.5 2±0 .16) ms和 ( 1.3 7± 0 .0 8) m s。结论 :改良法豚鼠 DPOAE检出率高 ,振幅大 ,各指标结果重复性好 ,适用于动物DPOAE的研究。     

Kinetic experiments with radionuclides concerning the perilymph-blood barrier in a guinea pig model

Summary Since 1950 many animal radiotracer experiments have been performed to study inner ear kinetics. For the most part in these studies, radionuclides were applied systemically, following which a discontinuous probing of inner ear fluids or of inner ear tissues was done. Two techniques have been developed in the Section for Experimental Otorhinolaryngology of the University of Würzburg. These have been adapted to the direct and continuous measurements of inner ear efflux kinetics for several hour periods. For this purpose, only a tiny amount of radiotracer need be applied directly to the inner ear. Experiments were done on the anesthetized guinea pig as an animal model. In the first technique, a collimator-detector system is focused precisely on the cochlea, which had been quickly resealed after application of the radionuclide bolus via two small holes in the basal turn of the cochlea. The second technique makes use of a perilymph cycling system, whereby a small outer volume includes a microcuvette with a socalled artificial round window. By this latter cycling technique, perilymph clearance kinetics of all kinds of radiotracers — with the exception of tritium labelled ones — can be measured. Calculations from clearance kinetics show that quite small particles with particle weights up to 100, such as the chlorine anion and the potassium cation, as well as urea, glycerol, pyruvate, and lactate, exhibit perilymphatic half-lives varying from 45 to 60 min. These half-live data are plausible in regard to cochlear blood flow measured previously via an independent technique developed by Angelborg et al. For particle weights distinctly beyond 100, half-lives increased gradually according to the operation of a perilymph-blood barrier. For a few tracers such as theophylline, nicotinamideadenine-dinucleotide, urografin, and biligrafin, individual effects are superimposed, giving rise to rather fast kinetics. In contrast, the ototoxic drugs ethacrynic acid and tobramycin exhibit a certain retardation in their clearance kinetics. Very small non-polar gaseous particles such as hydrogen and xenon show extremely short perilymphatic/cochlear half-lives. The half-life of hydrogen is about 4 min which accounts for a maximum clearance consistent with total cochlear blood flow.Dedicated to Professor Dr. Walter Kley, former head of the ENT Department, University of Würzburg     

Initial changes in the sensory hair-cell membrane following aminoglycoside administration in a guinea pig model

Summary This study demonstrates the initial changes affecting the sensory hair-cell plasma membranes in the vestibular end organs of gentamicin-treated guinea pigs by using a ruthenium red staining technique. First, 0.1 ml of a solution containing 5 mg gentamicin sulfate was injected into the middle ear. After 7 days, the sensory hair cell cilia were observed to be degenerating. The various stages of this degeneration process were classified into two types: the decrease in glycocalyx was designated type I fusion, while type II fusion was characterized by a bleb formation of the plasma membrane of the sensory hair cells, followed by a decrease in glycocalyx. The latter mechanism allowed plasma membrane contact, with subsequent fusion of the plasma membrane of neighboring sensory hair-cell cilia. The material also illustrates the degeneration of ciliary actin filaments. These findings suggest that the aminoglycoside affects both the glycocalyx and the plasma membrane, and that the decrease in glycocalyx may be the first sign of sensory hair-cell fusion.     

后半规管阻塞前后豚鼠前庭及耳蜗功能的动态变化

目的 探讨机械性后半规管阻塞前后豚鼠前庭和耳蜗功能的动态变化。方法 采用２０只豚鼠建立单侧后半规管阻塞的动物模型,观察手术前后眼震电图,听性脑干反应,耳声发射等变化。结果 术后第１天,第３天豚鼠正弦摆动刺激术侧眼震反应,明显减术,术后第５天起双侧眼震恢复正常。术后早期ＡＢＲ阈值一度升高,第５天达高峰,ＡＢＲ阈值平均升高４．５ｄＢ。ＤＰＯＡＥ反应幅度无明显改变。结论 后半规管阻塞能选择性地消除后半规     

豚鼠内耳Na,K-ATP酶α亚基异构体的表达

目的 研究豚鼠内耳组织中Na，K-ATP酶α亚基三种异构体αl、α2、α3的表达及其意义。方法 用小鼠抗大鼠Na，K-ATP酶α亚基异构体特异性单克隆抗体，采用免疫组化SP法观察豚鼠耳蜗、半规管、椭圆囊及球囊组织中Na，K—ATP酶α亚基三种异构体的表达模式。结果 αl亚基异构体广泛分布于内耳组织的各个部位，特别是上皮细胞和螺旋神经节细胞中，α2和α3亚基异构体则主要分布于螺旋神经节细胞、Corti器及血管纹。结论 Na，K—ATP酶亚基异构体在内耳不同部位的表达差异表明不同的内耳细胞转运Na^ 和K^ 的能力不同，它们共同作用参与保持内耳内环境的稳定。     

电刺激强度对豚鼠听神经兴奋性的影响

目的在不同电刺激下观察不同刺激强度的电诱发听性脑干反应(electricalevokedauditorybrainstemresponse,EABR)I波幅值的变化,评估刺激强度对豚鼠听神经兴奋性影响。方法选取健康短毛白色纯种红目豚鼠45只,标准电极分别插入豚鼠两侧鼓阶内大约4mm,靠近蜗尖两个电极作为刺激电极,随机选择一侧耳为刺激耳,另一侧耳为对照耳。选用二种不同的刺激强度[EABR阈上6dB(n=25)和阈上18dB(n=20)]电荷平衡双相脉冲电流,连续刺激2小时,刺激速率分别为200、1000PPS,观察刺激前和刺激后3小时内EABRI波幅值的变化。结果刺激强度为EABR阈上6dB、刺激速率为200PPS时I波幅值同刺激前相比升高20%,刺激速率为1000PPS时I波幅值较刺激者相比升高约7%;刺激强度为EABR阈上18dB时,应用200PPS刺激速率,I波的幅值在刺激后0分钟下降21%(P<0.05)、30分钟时下降11%(P<0.05)、60分钟时下降9%(P<0.05)、90分钟时下降7%(P>0.05)、120分钟时下降约2%(P>0.05)、150分钟时完全恢复正常;应用1000PPS的刺激速率,I波的幅值在刺激后0分钟下降56%(P<0.01)、30分钟时下降47%(P<0.01)、60分钟时下降58%(P<0.01)、90分钟时下降63%(P<0.01)、120分钟时下降约48%(P<0.01)、150分钟时下降43%(P<0.01)、180分钟时下降44%(P<0.01)。结论高速率和高强度连续电刺激导致EABRI波幅值持久下降反应了听神经的兴奋性变化不但受电刺激的速率影响,而且受电刺激的强度影响。