Lead and cadmium levels and balance and vestibular dysfunction among adult participants in the National Health and Nutrition Examination Survey (NHANES) 1999-2004

Background: Few studies have been conducted to identify risk factors for balance and vestibular dysfunction in general populations, but previous studies have reported evidence of adverse effects of lead and cadmium on balance control in high-risk groups.Objective: We evaluated the relationship between blood lead and cadmium levels and balance and vestibular dysfunction in a general population study.Methods: We analyzed data from the 1999–2004 National Health and Nutrition Examination Survey (NHANES) of 5,574 adults ≥ 40 years of age. Balance dysfunction was evaluated by the Romberg Test of Standing Balance on Firm and Compliant Support Surfaces, which examines the ability to stand unassisted using four test conditions to evaluate vestibular system, vision, and proprioception inputs that contribute to balance. Blood levels of lead and cadmium were measured by atomic absorption spectrometry. Associations were estimated using logistic regression models adjusted for potential confounders. Associations with time to loss of balance were estimated using adjusted Cox proportional hazard models.Results: The adjusted odds ratio (OR) for balance dysfunction in association with the highest quintile (3.3–48 µg/dL) versus the lowest quintile (< 1.2 µg/dL) of lead was 1.42 [95% confidence interval (CI): 1.07, 1.89]. The corresponding OR for cadmium (0.9–7.4 µg/L vs. < 0.2 µg/L) was 1.27 (95% CI: 1.01, 1.60). The adjusted hazard ratio for time to failure for the most physiologically challenging balance test among subjects with the highest vs. lowest quintiles of blood lead was 1.24 (95% CI: 1.04, 1.48). Cadmium levels were not associated with time to failure.Conclusions: Our findings suggest that blood lead and cadmium levels may be associated with balance and vestibular dysfunction in a general sample of U.S. adults.     

Potentiation of noise-induced hearing loss by low concentrations of hydrogen cyanide in rats.

Noise-induced hearing loss is the most prevalent occupational injury in the United States despite the adoption of clear permissible exposure limits and protocols for hearing conservation. This study identifies low-level chemical asphyxiant exposure as a risk factor capable of potentiating noise-induced hearing loss. Rats were exposed to 10, 30, and 50 ppm hydrogen cyanide (HCN) alone for 3.5 h (n = 28) or in combination with 2 h octave band noise exposure (100 dB(lin); n = 28). Additional groups received noise exposure alone (n = 16) and no treatment other than placement in an inhalation chamber with clean air and quiet (n = 16). Pure tone compound action potential (CAP) thresholds were determined 4 weeks following the exposure in order to assess pure tone auditory sensitivity and permanent threshold impairment. Cochleae from an additional 13 subjects were processed for light microscopy to permit assessment of hair cell loss. The results demonstrate that the noise exposure alone impaired CAP threshold by about 10 dB, averaged between 12-40 kHz, and produced a 5% loss of outer hair cells at the base of the cochlea, but no inner hair cell loss. The combined exposure to noise and HCN caused a cyanide dose-dependent CAP threshold impairment that exceeds the noise exposure alone. This effect reached statistical significance at a HCN level of 30 ppm. Combined exposure also produced more outer hair cell loss than noise alone. HCN alone did not cause significant hearing loss or hair cell loss. A risk assessment analysis was conducted for the auditory threshold data using benchmark dose software published by the U. S. EPA (BMDS version 1.3). A continuous model showed that the data could be described by a linear function. For a benchmark response corresponding to a 5 dB increase in auditory threshold above the effect of noise alone, the lower bound on the 95% confidence interval for the benchmark dose was 9 ppm. The benchmark dose that impaired auditory threshold 10% above the effect of noise alone had a lower bound of 2 ppm. The lower bound to the HCN dose that produced a 1 SD elevation in noise-induced hearing loss was 16 ppm. These exposure levels provide a range of concentrations below to slightly above the short-term exposure limit for HCN. However, if these levels are adjusted for an 8 h time-weighted average (TWA), the resulting levels are below the permissible exposure level (PEL) for HCN.     

Protective effects of apocynin on cisplatin‐induced ototoxicity in an auditory cell line and in zebrafish

Cisplatin is a very effective anticancer drug and generates reactive oxygen species (ROS) such as superoxide anions that can deplete antioxidant protective molecules in the cochlea. These processes result in the death of cochlear hair cells by induction of apoptosis. Apocynin, which is used as a specific nicotinamide adenine dinucleotide phosphate oxidase inhibitor, has a preventive effect for intracellular ROS generation. In this study, the effect of apocynin was investigated in a cochlear organ of Corti‐derived cell line, HEI‐OC1 cells, and in transgenic zebrafish (Brn3C: EGFP). To investigate the protective effects of apocynin, HEI‐OC1 cells were treated with various concentrations of apocynin and a 20 µm concentration of cisplatin, simultaneously. An in vivo study of transgenic zebrafish (Brn3C: EGFP) was used to investigate the protective effects of apocynin on cisplatin‐induced hair cell death. In an in vitro study, apocynin appeared to protect against cisplatin‐induced apoptotic features on Hoechst 33258 staining in the HEI‐OC1 cells. Treatment of the HEI‐OC1 cells with 100 µm of apocynin, significantly decreased caspase‐3 activity. Treatment of the cells with a 100 µm concentration of apocynin and a 20 µm concentration of cisplatin significantly decreased the intracellular ROS production. In the in vivo study, apocynin significantly decreased the TUNEL reaction and prevented cisplatin‐induced hair cell loss of the neuromasts in the transgenic zebrafish at low concentrations (125 and 250 µm ). These findings suggest that apocynin has antioxidative effects and prevents cisplatin‐induced apoptotic cell death in HEI‐OC1 cells as well as in zebrafish. Copyright © 2011 John Wiley & Sons, Ltd.     

药源性耳聋防治研究进展

为进一步了解耳毒性药物的种类和致聋机理,探讨预防和治疗耳聋的策略,对国内外近些年来报道的药源性耳聋相关文献进行整理、总结,药物的耳毒性与遗传、用药剂量、用药时间、给药途径、患者年龄和身体状况等有关。耳毒性药物涉及品种众多,造成的后果严重,应引起II缶床重视,加强临床合理用药,以预防为主,早发现,早治疗,减轻患者痛苦。     

Effect of Ligustrazine on Kanamycin Ototoxicity

Ｅｆｆｅｃｔ　ｏｆ　Ｌｉｇｕｓｔｒａｚｉｎｅ　ｏｎ　Ｋａｎａｍｙｃｉｎ　ＯｔｏｔｏｘｉｃｉｔｙＳＨＥＷａｎ－ｄｏｎｇ（佘万东）ａｎｄＣＨＥＮＺｈａｏ－ｈｅ（陈兆和）（ＤｅｐａｒｔｍｅｎｔｏｆＯｔｏｌａｒｙｎｇｏｌｏｇｙ，ＡｆｆｉｌｉａｔｅｄＤｒｕｍＴ...     

银杏叶提取物与去铁胺合用防治顺铂耳毒性实验研究

目的银杏叶提取物-金纳多(extract of Ginkgo Biloba leaves injection,EGb)和铁螯合剂-去铁胺(Deferoxamine,DFO)联合应用对抗顺铂(Cisplatin,CDDP)耳毒性的作用。方法将豚鼠随机分为CDDP组、EGb组、DFO组、EGb+DFO组及对照组,测定听性脑千反应(auditory brain—stem response,ABR)、血清超氧化物歧化酶(superoxide dismutase,SOD)活性和丙二醛(MDA)含量及应用光镜、及扫描电镜技术,观察用药前后各指标的变化。结果CDDP组动物ABR阈值较其他各组明显升高(P<0．01),其余各组间差异不显著(P>0．05)。血清SOD活性和MDA含量检测表明,CDDP组血清SOD活性较对照组明显降低(P<0．01),MDA含量显著升高(P<0．01),其他组较对照组则差异无显著性(P>0．05)。耳蜗扫描电镜显示EGb+DFO组和DFO组比CDDP组毛细胞受损程度明显为轻,EGb组较CDDP组毛细胞受损程度略微减轻。结论DFO与EGb合用,可有效减轻CDDP的耳毒性作用,其效果优于单独应用EGb,与单独应用DFO效果相当,二者合用还可能减轻顺铂的骨髓抑制副作用。结果提示铁离子参与的自由基反应可能是顺铂耳毒性机制之一。     

铂类的耳毒性

铂类化合物的耳毒性具有初期症状隐匿 ,不可逆性和严重影响生活质量等特点 ,逐渐为临床医师所关注。该文对其发病情况 ,病理学改变 ,临床特征和防治措施等加以综述。