白藜芦醇拮抗庆大霉素耳毒性的实验研究

目的观察白黎芦醇（resveratrol,Res）对抗庆大霉素耳毒性的作用.方法将豚鼠随机分为庆大霉素（gentamicin, GM）组、白藜芦醇剂量I＋GM组 （ResI ）、白黎芦醇剂量II＋GM组（ResII）、白黎芦醇剂量III＋GM组（ResIII）及对照组.采用听性脑干反应（ABR）、耳蜗铺片及透射电镜技术,观察用药前后各组动物听阈及耳蜗毛细胞形态学改变,并检测血清丙二醛、超氧化物岐化酶含量、肾功能以及庆大霉素血药浓度.结果 ResIII组血液中丙二醛较GM组明显减少（P〈0.05）,GM＋Res各组超氧化物歧化酶活性均明显高于GM组（P〈0.05）,同时GM组1、8 kHz ABR 4 周平均阈移与ResIII剂量组间差异显著（P〈0.05）.形态学改变与听力变化一致.Res对庆大霉素血药浓度没有影响.结论大剂量Res能有效减轻GM的耳毒性作用,且不影响庆大霉素的抗菌作用.     

庆大霉素耳毒性的临床调查

目的：调查临床使用庆大霉素所致听力损伤患者的发生率及特点。方法：平均使用庆大霉素1120mg，最长随访76天，采用纯音测听和听性脑干反应检查患者使用庆大霉素前后听力变化。结果：发生吸力损伤18例（26．5％），多数表现在高频区，且有4例为单耳损伤。一例有主观症状者治疗后耳聋减轻。结论：临床使用庆大霉素治疗期间及用药前后应了解听力情况和变化，并及时发现和处理听力损伤。     

庆大霉素对豚鼠耳肾毒性的相关性实验研究

目的 探讨豚鼠庆大霉素耳性与肾毒性的关系。方法 通过ＡＢＲ测试,耳蜗铺片毛细胞片数,血液庆大霉素药代动力学分析,血ＢＵＮ、Ｃｒ值测定,肾标光镜下观察等方法,观察肌注庆大霉互后豚鼠的耳蜗功能及肾功能变化。结果 肌注庆大霉素二周组ＡＢＲ的ＩＶ波反应阈阈移明显高于肌注庆大霉素一周组及其生理盐水对照组。光镜下耳蜗铺片毛细胞计数二周组毛细胞缺失数明显多于一周组对于对照组。肌注纱二周组的血清庆大霉素清除率明显     

应用畸变产物耳声发射观察褪黑素对庆大霉素耳毒性拮抗作用

目的 研究褪黑素（melatonin,MLT)对庆大霉素（gentamicin,GM)耳毒性的拮抗作用。方法 实验分为GM组，MTL＋GM组及生理盐水对照组，采用豚鼠畸变产物耳声发射（distortion product otoacoustic emission,DPOAE)，观察用药后DPOAE幅值及I／O曲线斜率的变化。结果 GM组用药3后，4，6，8kHz DPOAE幅值同对照组相比有显著性差异（P＜0．01）；I／O曲线斜率变小，在4，6，8kHz与对照组相比有显著性差异（P＜0．01）。GM＋MLT组用药后各频率段DPOAE幅值，与对照组相比地显著性差异；I／O曲线斜率无明显改变，同对照组相比无显著性差异（P＞0．05）。结论 MLT能有效拮抗庆大霉素的耳毒性作用。     

聚DL—天冬氨酸对庆大霉素耳毒性拮抗作用的实验研究

目的 研究聚ＤＬ－天冬氨酸（ＰＡＡ）对Ｆ－３４４大鼠庆大霉素（ＧＭ）耳毒性的拮抗作用。方法 选用健康Ｆ－３４４大鼠５０只,随机分４组：Ｉ为ＧＭ、Ⅱ为ＰＡＡ＋ＧＭ、Ⅲ为ＰＡＡ、Ⅳ为生理盐水对照组;通过观测４组大鼠不同时期、不同频率听性脑干反应（ＡＢＲ）阈值的改变;计数耳蜗毛细胞死亡率,以观察ＰＡＡ对Ｆ－３４４大鼠ＧＭ耳蜗毒性的拮抗作用;用双向扩散血清培养基检测法观察ＰＡＡ对ＧＭ抗菌活性的影响。结果     

庆大霉素肾毒性和耳毒性的关系实验研究及其与中…

我们应用血浆尿素氮，血浆肌酐，脑干电位，肾脏组织病理和耳蜗铺片观察庆大霉素引起的豚鼠肾功能和听功能改变，以及肾小管和耳蜗毛细胞的病理改变，发现用药期间，在出现耳毒作用之前先出现了肾毒作用，在出现耳毒作用时豚鼠表现为中医肾虚证候。实验证实肾功能的变化的是耳中毒的先兆，提示临床上应用庆大霉素过程中，可以通过监测肾功能指标，若发现肾功能损害可以及早停药，可防止中毒性聋的发生；且发现实验结果与中医肾主耳理     

谷胱苷肽治疗早期庆大霉素耳中毒实验观察

目的了解庆大霉素(GM)早期耳中毒后,应用谷胱苷肽(GSH)治疗能否改善听力。方法选听力正常豚鼠30只,随机分3组,观察组12只(肌注GM100mg.kg-1*d-1,一旦ABR阈移10dB以上立即停药观察),治疗组12只(按观察组用药,停药,停药后再用GSH5天),对照组6只(仅肌注等量盐水)。所有动物在用药前后均检测ABR之波Ⅲ反应阈。停药二周后处死作耳蜗铺片。结果观察组停用GM二周后复查ABR阈移继续增大(P＜0.01)。治疗组停用GM二周后无明显阈移(P＞0.05)。对照组则前后无变化。耳蜗毛细胞形态变化与功能变化基本一致。结论早期GM耳中毒一旦出现ABR阈移即使立即停药听力损害仍将继续加重;GSH能阻止在耳蜗内蓄积的GM对听力进一步损害。     

聚DL-天冬氨酸对庆大霉素耳毒性拮抗作用的实验研究

目的　研究聚ＤＬ天冬氨酸（ｐｏｌｙ ＤＬａｓｐａｒｔｉｃ ａｃｉｄ,ＰＡＡ） 对Ｆ３４４ 大鼠庆大霉素（ｇｅｎｔａｍｉｃｉｎ,ＧＭ） 耳毒性的拮抗作用。方法　选用健康Ｆ３４４ 大鼠５０ 只,随机分４ 组：Ⅰ为ＧＭ、Ⅱ为ＰＡＡ＋ ＧＭ、Ⅲ为ＰＡＡ、Ⅳ为生理盐水对照组;通过观测４ 组大鼠不同时期、不同频率听性脑干反应（ａｕｄｉｔｏｒｙ ｂｒａｉｎｓｔｅｍ ｒｅｓｐｏｎｓ,ＡＢＲ）阈值的改变;计数耳蜗毛细胞死亡率,以观察ＰＡＡ对Ｆ３４４ 大鼠ＧＭ 耳蜗毒性的拮抗作用;用双向扩散血清培养基检测法观察ＰＡＡ 对ＧＭ 抗菌活性的影响。结果　Ⅰ组短纯音１０ ｋＨｚ、８ ｋＨｚ ＡＢＲ阈值与其他３ 组差异有显著性（ Ｐ＜ ０．０１） ,给药１８ ｄ 耳蜗毛细胞死亡率与其他３ 组间差异也有显著性（ Ｐ＜０ ．０１）。结论　ＰＡＡ对庆大霉素的耳毒性具有拮抗作用,且不减低其抗菌活性。     

一氧化氮对庆大霉素耳毒性的影响

目的研究耳蜗内不同水平的一氧化氮(NO)含量对庆大霉素(GM)耳毒性的影响.方法将实验动物豚鼠随机分为GM组;庆大霉素加左旋精氨酸(GM加L-Arg)组;庆大霉素加NG-单甲基-L-精氨酸(GM加L-NMMA)组和正常对照组.实验过程中观察动物体重变化,检测ABR反应阈;取标本检测血清和耳蜗组织NO含量,耳蜗铺片观察毛细胞损失程度.结果对照组动物体重增加明显,各实验组体重增加缓慢,其中GM加L-Arg组体重略有下降.实验第4周,GM加L-Arg组ABR反应阈升高明显,与GM组比较有统计学意义(P<0.05),GM加L-NMMA组ABR反应阈升高较少,与GM组比较有统计学意义(P<0.05).GM加L-Arg组血清和耳蜗NO含量明显升高,GM加L-NMM A组NO含量升高不明显,与GM组比较差异具有显著性(P<0.05).耳蜗铺片各组毛细胞损失程度与ABR变化相对应.结论增加耳蜗NO含量可增加GM耳毒性,减少耳蜗NO含量可减轻GM耳毒性.     

Delayed nerve repair is associated with diminished neuroenhancement by FK506

OBJECTIVES/HYPOTHESIS: The immunosuppressive agent FK506 has been shown in many studies to enhance nerve regeneration and to accelerate functional recovery after immediate nerve repair. However, in clinical practice the diagnosis and treatment of patients with peripheral nerve injuries is often delayed. The study investigated whether FK506 would retain its neuroregenerative properties when nerve repair and initiation of FK506 therapy were delayed for 7 days. STUDY DESIGN: In vivo laboratory study. METHODS: Thirty-two Lewis rats underwent tibial nerve transection and were randomly assigned to four experimental groups: immediate repair with FK506 treatment, immediate repair without FK506 treatment, 7-day delayed repair with FK506 treatment, and 7-day delayed repair without FK506 treatment. Treated animals received daily subcutaneous injections of 2 mg/kg FK506. Serial walking track measurements were performed at 14, 16, and 18 days after nerve repair. On day 18 after repair, peripheral nerves were injected with a fluorescent tracer for retrograde labeling. On day 21, peripheral nerves and spinal cords were harvested for histomorphometric analysis and motor neuron cell body counts, respectively. RESULTS: Animals that underwent immediate repair with FK506 had significantly higher fiber counts and percentages of nerve than the other three groups (P <.05) but did not show statistically significant earlier functional recovery. The remaining three groups had intermediate levels of nerve regeneration that were not significantly different. Retrograde abled motor neurons counts were decreased in animals with delayed nerve repair that received no FK506 (P <.05). CONCLUSION: In a rat tibial nerve transection model, the neuroregenerative effects of FK506 diminished markedly when repair and initiation of FK506 therapy were delayed by 7 days.     

Cochlear ototoxicity of chlorhexidine gluconate in cats

Summary Chlorhexidine gluconate is a derivative of chlorhexidine and is a popular desinfectant with a strong bactericidal action that is widely used for preoperative sterilization in ear surgery. The purpose of this investigation is to ascertain the potential ototoxity of this agent. After topically applying chlorhexidine gluconate solutions to the middle ear cavities of 12 cats, we observed the excised cochleas using both scanning and transmission electron microscope studies. Either 0.05% or 2% chlorhexidine gluconate solutions were infused into the right ear of the test animal through one of two tubes chronically installed in the tympanic bullae. The left ears were utilized as controls and were infused with sterilized physiological saline. The solutions were administered once every other day for three separate infusions. Nine animals were decapitated 7 days after the third application, while the other three animals were sacrificed at 4 weeks. In the 2% chlorhexidine group, we found that hair cells in the organ of Corti had degenerated and had lost their hair bundles over a wide range. This pathology was more marked in the lower cochlear turns. In the animals sacrificed at 4 weeks, the injuries present seemed to have progressed. Even at a clinical concentration of 0.05%, chlorhexidine caused intracellular degeneration but with little surface damage. Our findings would suggest a cause of hearing loss when chlorhexidine is used clinically in the ear.     

鼓室内注射庆大霉素治疗难治性梅尼埃病

目的探讨鼓室内注射庆大霉素治疗难治性梅尼埃病的方法、疗效及副反应。方法对10例(11耳)难治性梅尼埃病患者行鼓室内注射庆大霉素治疗,然后分析其眩晕控制情况以及听力的变化。结果10例患者均随访2年以上,眩晕控制A级8例,B级2例;听力改善B级1例,C级9例。结论鼓室内注射庆大霉素是治疗难治性梅尼埃病的有效方法,值得临床进一步深入研究、探讨。     

利尿酸与庆大霉素耳毒作用协同影响的实验研究

通过给72只豚鼠分别单独注射利尿酸（EA)、庆大霉素（GM）和合并注射EA、GM后，观察三组豚鼠前庭功能、听力改变、血清和外淋巴中庆大霉素浓度以及内耳显微和亚显微结构的改变，发现合并使用利尿酸和庆大霉素可以加重庆大霉素耳中毒，其可能原因为利尿酸增加了庆大霉素在外淋巴中的蓄积。     

庆大霉素对小鼠螺旋神经节神经元电生理特性的影响

目的 探讨庆大霉素对小鼠耳蜗螺旋神经节神经元细胞电生理特性的影响及其意义。方法 应用全细胞电压钳技术研究庆大霉素对急性酶分离小鼠螺旋神经节神经元细胞膜上的钾、钠离子通道电流的峰值的影响．与细胞外液中庆大霉素浓度的关系，以及庆大霉素洗脱后电流的恢复情况。结果 庆大霉素能抑制电压依赖性钾通道，但不能抑制电压依赖性钠通道，其钾通道抑制作用与细胞外液中庆大霉素的浓度呈剂量依赖性，庆大霉素洗脱后电流恢复不完全。结论 庆大霉素通过抑制螺旋神经节神经元细胞的钾离子通道而产生耳毒性。     

黄芩苷对庆大霉素致小鼠耳毒性作用的影响

目的探讨黄芩苷(baicalin,BA)拮抗庆大霉素(gentamycin,GM)致小鼠耳蜗螺旋神经节(spiraIganglion,SG)细胞毒性作用的机理.方法用紫外分光光度法分别测定各实验组SG细胞内总超氧化物歧化酶(T-SOD)活性,谷胱甘肽过氧化物酶(GSH-PX)活性以及丙二醛(MDA)含量.结果黄芩苷可显著抑制GM所导致的SG细胞中T-SOD和GSH-PX活性降低及MDA含量升高.结论黄芩苷可清除耳蜗螺旋神经节细胞内氧自由基,抑制脂质过氧化反应.     

Gentamycin im Verteilungsgleichgewicht zwischen Serum,Perilymphe und Liquor beim Meerschweinchen nach Dosierung im therapeutischen Bereich

Zusammenfassung Gentamycindosierungen im therapeutischen Bereich führen ebenso wie höhere Dosierungen bei gleichbleibend hohen Serumspiegeln zu einem Verteilungsgleichgewicht zwischen Serum, Perilymphe und Liquor. Nach hohen Dosierungen resultieren Perilymphspiegel, die im Verhältnis zum Serumspiegel relativ niedriger bleiben als die Perilymphspiegel nach geringerer Dosierung. Das Verteilungsgleichgewicht wird bei einer Dosierung, die zu Serumkonzentrationen im vermuteten ototoxischen Grenzbereich führt, nach ca. 7 Std erreicht. Danach steigt die Innenohrkonzentration nicht weiter an.Die Serumkonzentration im steady state ist immer größer als die Perilymphkonzentration, diese immer größer als die Liquorkonzentration.Dipl.-Mathematiker     

畸变产物耳声发射在豚鼠庆大霉素中毒性耳聋早期监测中的作用

目的 研究畸变产物耳声发射（DPOAE）在豚鼠庆大霉素（gentamycin,GM）中毒性耳聋早期监测中的作用.方法经畸变产物耳声发射检测及耳廓反射正常的豚鼠16只（31耳）随机分成两组.GM组8只（16耳）每天肌肉注射GM100 mg/kg,连续10天;对照组8只（15耳）肌肉注射等量0.9%生理盐水10天.每组在肌肉注射前、注射第3、7天测试DPOAE,对1、2,4、6 kHz的DPOAE幅值进行比较分析.结果①对照组豚鼠在肌肉注射0.9%生理盐水的第3、7、10天与注射前比较,DPOAE引出率为100%,1、2,4、6 kHz的幅值差异无统计学意义（P＞0.05）.②GM组在肌肉注射庆大霉素第3天DPOAE的幅值与注射前及对照组比较,4、6 kHz处幅值差异有统计学意义（P＜0.05）;肌肉注射庆大霉素第7天,2,4、6 kHz处幅值差异有统计学意义（P＜0.05）.结论肌肉注射庆大霉素第3天即可发现豚鼠DPOAE 4 kHz以上的高频听力损害,第7天发现4 kHz以下的低频听力损害.     

Tacrolimus and mycophenolate mofetil provide effective immunosuppression in rat laryngeal transplantation

OBJECTIVES/HYPOTHESIS: Tacrolimus is efficacious in several transplantation settings. Some studies have demonstrated improved results using combination therapy with mycophenolate mofetil. Our primary objective was to evaluate the efficacy and optimal dosing of tacrolimus in preventing rejection, using an established rat model of laryngeal transplantation. Further, the ability of mycophenolate to allow lower dosing of tacrolimus while achieving equivalent immunosuppression was investigated. STUDY DESIGN: A dosage efficacy study with 10 experimental arms was conducted. METHODS: Dosage groups were 0.1, 0.2, 0.3, and 0.6 mg/kg tacrolimus alone and 0.1 mg/kg tacrolimus combined with 15 mg/kg mycophenolate mofetil, 0.1 mg/kg tacrolimus combined with 30 mg/kg mycophenolate mofetil, 0.1 mg/kg tacrolimus combined with 40 mg/kg mycophenolate mofetil, 0.2 mg/kg tacrolimus combined with 15 mg/kg mycophenolate mofetil, 0.2 mg/kg tacrolimus combined with 30 mg/kg mycophenolate mofetil (30 d only), and 0.2 mg/kg tacrolimus combined with 40 mg/kg mycophenolate mofetil. Each group contained 8 to 10 rats. Grafts were harvested for histopathological analysis on day 15 or 30 after transplantation. Histopathological appearance of the graft was blindly graded according to an established scale. Dosage groups were compared on rejection score using Wilcoxon's rank sum test and the Jonckheere-Terpstra test for trend. RESULTS: There was a significant association between increasing dose of tacrolimus and decreasing rejection score at both 15 and 30 days (P <.001). In the groups treated with 0.1 mg/kg T, an increasing dose of mycophenolate was associated with lower rejection scores at both 15 and 30 days (P =.001). In the group treated with 0.2 mg/kg T, there was no evidence that the addition of mycophenolate resulted in lower rejection at 15 days. However, at 30 days, combination therapy with increasing doses of mycophenolate was associated with decreasing rejection score (P =.002). CONCLUSIONS: Tacrolimus is an effective immunosuppressive agent for laryngeal transplantation. Mycophenolate mofetil allows lower doses of tacrolimus to be used while preserving graft viability in the early post-transplantation period.     

术前消毒剂对小鼠术后近期听性脑干反应的影响

目的观察术前消毒剂醋酸氯己定(安尔碘)、聚维酮碘(点而康)、乙醇、苯扎溴铵酊对听功能的影响。方法 25只ABR反应阈正常的ICR小鼠随机分为5组,每组5只。将醋酸氯己定、聚维酮碘、乙醇、苯扎溴铵酊及生理盐水分别注入各组双耳中耳腔内,5min后吸出消毒剂,24h后观察小鼠8、16、24、32kHz短纯音ABR反应阈变化。结果醋酸氯己定、聚维酮碘、乙醇、及苯扎溴铵酊组小鼠8、16、24、36kHz ABR反应阈均较实验前明显升高(均为P<0.05),而生理盐水对照组实验前后ABR反应阈无显著变化。结论皮肤消毒剂进入中耳可导致小鼠听力下降,因此,术前消毒时应避免消毒剂通过外耳道及穿孔的鼓膜进入中耳。