Chronic arsenic exposure and urinary 8-hydroxy-2'-deoxyguanosine in an arsenic-affected area in Inner Mongolia, China

OBJECTIVE: Recent studies have shown that generation of reactive oxidants during arsenic metabolism can play an important role in arsenic-induced injury. The purpose of this study was to examine the relationship between arsenic in drinking water and oxidative stress in humans by measuring 8-Hydroxy-2'-deoxyguanosine (8-OHdG). METHODS: We performed a cross-sectional study in an arsenic-affected village in Hetao Plain, Inner Mongolia, China. A total of 134 of the 143 inhabitants (93.7%) of the village participated in the study. The levels of 8-OHdG, arsenic and its metabolites were measured in urine collected from the participants. Regression analyses were performed to investigate the relationship between arsenic species and 8-OHdG levels in urine. RESULTS: In the polluted village, monomethylarsenic was significantly higher in subjects with arsenic dermatosis than those without dermatosis despite no difference in mean levels of arsenic in well water between both types of subject. For subjects with arsenic dermatosis, arsenic species and metabolites in urine are significantly associated with 8-OHdG, while there was no statistically significant relationship for subjects without arsenic dermatosis. For all residents of the polluted village, the levels of dimethylarsenic and 8-OHdG were significantly higher for those who had been exposed to well water for more than 12 years. CONCLUSIONS: These results provide evidence of a link between exposure to arsenic from drinking water and oxidative stress, which may play an important role in arsenic-involved injuries.     

The prevalence of subjective symptoms after exposure to arsenic in drinking water in Inner Mongolia,China

BACKGROUND: In Inner Mongolia, China, more than 300,000 people are chronically exposed to arsenic via their drinking water. We have previously reported that the prevalence of arsenical dermatosis was as high as 40% in the Hetao Plain area. However, the association between exposure to arsenic in drinking water and adverse health effects has not been fully examined. The purpose of this study was to examine the association between exposure to arsenic and prevalence of subjective symptoms. METHODS: A cross-sectional study was carried out in 431 residents of an arsenic-affected village and 189 residents of an arsenic-free village in 1996. Health-related interviews and physical examinations were conducted. The odds ratio for each subjective symptom was estimated, comparing residents of arsenic-free and affected villages. RESULTS: An arsenic level of 50+ microg/L was found in 90.6% of wells in the arsenic-affected village. Adjusted odds ratios of subjective symptoms, including coughs (odds ratio [OR] = 12.8, 95% confidence interval [CI]: 6.4-25.6), stomachaches (OR = 5.8, 95% CI: 3.6-9.4), palpitations (OR = 3.6, 95% CI: 1.5-8.2), urination problems (OR = 14.7, 95% CI: 3.3-65.5) and spontaneous abortions (OR = 2.7, 95% CI: 0.8-8.4), were markedly higher amongst residents of the arsenic-affected village, including those without arsenic dermatosis. CONCLUSIONS: The present study shows a high prevalence of subjective symptoms amongst residents of an arsenic-affected village. Symptoms occurred in people with and without arsenic dermatosis. Our findings suggest that symptoms other than dermatosis should be considered when a clinical diagnosis of arsenic toxicosis is made.     

砷作业工人神经电生理研究

本文对50名砷中毒、25名砷接触工人进行了肌电和神经传导速度的检查。对42名对照者仅作了神经传导速度的检查。发现慢性中毒组纤颤波的检出率为34%,砷接触组为8%。砷中毒组的正中神经,腓肠神经和尺神经SCV 显著减慢;尺神经MCV 延长;而砷接触组仅见尺神经MCV 减慢。以神经传导速度最低限((?)-2SD)进行分析,其减慢的检出率较高。长期接触砷可致周围神经源性损害,恢复较慢,感觉神经传导速度减慢似为多见。神经电生理的测定可作为砷中毒的一项诊断指标,可检出早期砷对周围神经的损害。     

苯对接触工人外周神经传导速度的影响

[目的 ]探讨苯对周围神经系统的影响。 [方法 ]对苯接触观察对象 13人、苯中毒者 14人为接触组 ,另选无毒物接触史的工人 48人为对照组 ,应用神经肌电图检测方法进行运动和感觉神经传导速度测定。 [结果 ]接触组尺神经及下肢腓浅神经感觉传导速度显著慢于对照组 (P <0 .0 5 ) ,其余所检神经传导速度与对照组相比差异无显著性 (P >0 .0 5 )。接触组下肢腓浅神经感觉传导速度异常率显著高于对照组。正中神经远端潜伏期较对照组明显延长 (P <0 .0 5 )。[结论 ]苯对周围神经存在一定程度的影响 ,感觉神经传导速度对于诊断周围神经病的价值优于运动神经传导速度     

奥克托今对作业工人周围神经传导速度的影响

目的 探讨奥克托今（HMX）对作业工人周围神经传导速度的影响。方法 选取76名接触HMX的作业人员为接触组。并以38名不接触HMX和神经毒物质的健康人作为对照。按标准方法测定正中神经，尺神经，腓总神经运动传导速度和感觉传导速度及运动潜伏期，同时测定车间空气中HMX浓度。并对不同接触浓度和不同作业工龄进入地比较。结果 接触组腓总神经远端运动潜伏期明显延长，正中神经近端感觉传导速度明显减慢，高浓度接触组正中神经，尺神经远端感觉神经潜伏期较低浓度组明显延长。20年以上工龄组正中神经，尺神经，腓总神经运动传导速度和正中神经感觉传导速度明显减慢，接触组腓总神经运动传导速度异常检出率明显高于对照组。结论 HMX对下肢神经传导速度影响明显，并与接触。浓度和作业工龄长短关系密切，但HMX影响周围神经传导速度的机制还不清楚，是否与神经递质释放有关，有待进一步探讨。     

Mental health burden amongst inhabitants of an arsenic-affected area in Inner Mongolia, China

Inner Mongolia, China, is an area with high levels of arsenic. The adverse health effects resulting from chronic arsenic exposure include skin keratosis, vascular diseases and cancers. However, the effects of arsenic exposure on mental health have not received much attention. The purpose of this study was to examine the effects of arsenic poisoning on the mental health of the inhabitants of an arsenic-affected area. We performed a cross-sectional study at two villages in Hetao Plain, Inner Mongolia. The populations of both villages were similar in age, sex, lifestyle, socioeconomic conditions, and geographic location. One hundred and thirty four (93.7%) of the 143 inhabitants in the arsenic-affected village and 36 (76.6%) of the 47 inhabitants in the arsenic-free village participated in the study. Subjects with a 30-item version of General Health Questionnaire score of 9 or more were defined as having symptoms of distress. The multiple logistic analyses showed that the mental health of the subjects in the arsenic-affected village was worse than in those in the arsenic-free village (OR=2.5, 95% CI=1.1-6.0). The effect of arsenic on mental health in arsenic-affected areas deserves further investigation. The mental health burden in arsenic-affected areas should be considered in the wider context of public and community health.     

Arsenic contamination of groundwater and its health impact on residents in a village in West Bengal, India

An in-depth study was carried out in Rajapur, an arsenic-affected village in West Bengal, India, to determine the degree of groundwater contamination with arsenic and the impact of this contamination on residents. The flow injection hydride generation atomic absorption spectrometry (FI-HG-AAS) method was used to measure arsenic concentrations in water and biological samples. Dermatologists recorded the dermatological features of arsenicosis. Out of a total of 336 hand-pumped tube-wells in Rajapur, 91% (307/336) contained arsenic at concentrations > 10 microg/l, and 63% (213/336) contained arsenic at > 50 microg/l. The type of arsenic in groundwater, the variation in concentrations of arsenic as the depth of tube-wells changed, and the iron concentration in the wells were also measured. Altogether 825 of 3500 residents were examined for skin lesions; of these, 149 had lesions caused by exposure to arsenic. Of the 420 biological samples collected and analysed, 92.6% (389) contained arsenic at concentrations that were above normal. Thus many villagers might be subclinically affected. Although five arsenic-filtering devices had been installed in Rajapur, it appears that villagers are still exposed to raised concentrations of arsenic in their drinking-water. Detailed village-level studies of arsenic-affected areas in West Bengal are required in order to understand the magnitude of contamination and its effects on people. Villagers are ill-informed about the dangers of drinking arsenic-contaminated water. The contamination could be brought under control by increasing community awareness of the dangers and implementing proper watershed management techniques that involve local people.     

75例2型糖尿病患者神经传导速度检测分析

目的:对2型糖尿病患者进行神经传导速度(NCV)检测,为糖尿病并发周围神经病变的早期诊断与治疗提供一项客观检测指标.方法:采用Viking IV肌电/诱发电系统仪对75例2型糖尿病患者的运动神经传导速度(MCV)和感觉神经传导速度(SCV)进行测定.结果:75例共测定周围神经300条,总异常率为54.3%,其中SCV的异常率(63.3%)高于MCV的异常率(45.3%),异常率比较有非常显著性差异(x2=9.79,P＜0.01).NCV异常率与年龄、上下肢无明显关系,而与病程长短有关.结论:NCV的改变是诊断糖尿病周围神经病变重要的早期客观指标,可作为糖尿病患者常规检查项目之一.     

Evidence for induction of oxidative stress caused by chronic exposure of Chinese residents to arsenic contained in drinking water

Exposure of experimental animals or cultured cells to arsenic induces oxidative stress, but, to date, no examination of this phenomenon in humans has been reported. In this study we conducted a cross-sectional study in Wuyuan, Inner Mongolia, China, to explore the relationship between chronic arsenic exposure from drinking water and oxidative stress in humans. Thirty-three inhabitants who had been drinking tube-well water with high concentrations of inorganic arsenic (mean value = 0.41 mg/L) for about 18 years constituted the high-exposure group, and 10 residents who lived nearby but were exposed to much lower concentrations of arsenic in their drinking water (mean value = 0.02 mg/L) were selected as the low-exposure comparison group. Results of the present study indicated that although the activity for superoxide dismutase (SOD) in blood did not differ significantly between the two groups, the mean serum level of lipid peroxides (LPO) was significantly higher among the high-exposed compared with the low-exposed group. Elevated serum LPO concentrations were correlated with blood levels of inorganic arsenic and its methylated metabolites. In addition, they showed an inverse correlation with nonprotein sulfhydryl (NPSH) levels in whole blood. The subjects in the high-arsenic-exposure group had mean blood NPSH levels 57.6% lower than those in the low-exposure group. Blood NPSH levels were inversely correlated with the concentrations of inorganic arsenic and its methylated metabolites in blood and with the ratio of monomethylarsenic to inorganic arsenic. These results provide evidence that chronic exposure to arsenic from drinking water in humans results in induction of oxidative stress, as indicated by the reduction in NPSH and the increase in LPO. Some possible mechanisms for the arsenic-induced oxidative stress are discussed.     

Increasing awareness of arsenic in Bangladesh: lessons from a public education programme

Experts are making a major effort to find technical solutions to the serious public health problems posed by arsenic in drinking water in Bangladesh, but public education strategies receive less systematic attention. This article presents the findings of a study evaluating the impact of a 1999 campaign by the 18 District Towns Project to educate the public about the arsenic problem in six Bangladesh towns, where half of the population was estimated to be using arsenic-contaminated domestic water: (1). Water users were advised not to consume arsenic-affected tube-well water; (2). A simple, temporary water treatment method was recommended for those using such water, if they had no safe alternative source; (3). Caretakers of tube-wells having arsenic-free water were advised to share their water sources with others. This evaluation study, utilizing a combination of quantitative and qualitative social research methods, found those influenced by the programme to have higher awareness levels and significantly lower levels of risk behaviour than others. Yet more than half of the at-risk, programme-influenced survey respondents were found still to be drinking (57%) or cooking with (54%) arsenic-affected water. Despite the fact that the campaign did not have a satisfactory public health impact, the experience can inform future efforts to educate the Bangladeshi public about arsenic. One finding is widespread confusion about trusted tube-well water being newly labelled as 'unsafe'. Some think the problem is in the hand pumps themselves. Awareness of life threatening danger from arsenic contamination was found to be low. Learning points from this experience are: the value of explaining together with water testing; giving people opportunities to ask questions; repeating messages; continuing to educate children about the serious risks of consuming surface water; conducting community-wide education programmes for people of all ages; and evaluating the impact of specific public education strategies. Respecting such principles in public information campaigns will greatly help the public to benefit from future technical developments.     

20名手传振动作业工人的神经肌电图分析

目的探讨手传振动对作业工人周围神经的损害情况。方法对20名从事手传振动作业工人和30名无接触职业危害的健康成人进行神经肌电图检查分析。结果①MCV检测结果显示正中神经运动传导远端潜伏期延长（占85．0％）、MCV减慢（占35．0％）（P〈0．01）;②SCV捡测结果显示正中神经SCV减慢（占40．0％）、尺神经SCV减慢（占30．0％）（P〈0．01）;③肌电图检查结果表现为小力收缩时多相电位增多（占42．5％）及安静时出现纤颤电位（占15．0％）（P〈0．05或P〈0．01）。结论振动对作业工人周围神经损伤明显,神经肌电图检查最早表现为正中神经运动传导远端潜伏期延长,随着损伤加重,进一步出现神经传导速度减慢,运动和感觉同时受累。     

Assessment of the peripheral, central, and autonomic nervous system function in styrene workers.

To investigate the effects of styrene exposure on peripheral, central, and autonomic nervous system functions in man, we measured the distribution of nerve conduction velocities (DCV), short-latency somatosensory evoked potentials (SSEP), and variability in electrocardiographic R-R interval (CVRR) as well as conventional sensory and motor median nerve conduction velocities (SCV and MCV) in eleven styrene-exposed workers. The styrene workers' urinary phenylglyoxylic acid levels ranged from 31 to 419 (mean 169) mg/g creatinine at the end of the work shift on the examination day (estimated exposure to styrene of 22 ppm in air). Control subjects, matched to each styrene worker by sex and age, were selected from healthy adults without cardiovascular, neurologic and other potentially confounding disorders. In the styrene workers, we found that the V80 velocity of the DCV, below which 80% of active nerve fibers lie, and the SCV were both significantly slowed; the CVRR was also significantly reduced. There were no significant differences in SSEP latencies, MCV, or heart rate between the exposed workers and controls. These data, despite the small sample size, suggest that styrene affects the faster myelinated fibers of the peripheral sensory nerves, and that it also affects autonomic nervous activity.     

慢性酒精中毒性周围神经病的神经电生理检查分析

目的探讨神经传导速度（NCV）和H反射对慢性酒精中毒性周围神经病（CAPN）的诊断价值。方法选择慢性酒精中毒性周围神经病患者和健康对照者各60例,用肌电图诱发电位仪检测正中、尺、腓、胫神经NCV,并在胭窝引出H反射。结果患者组的NCV及H反射与对照组比较异常率明显增高（P〈0．01）;下肢运动神经传导速度（MCV）异常率高于上肢;感觉神经传导速度（SCV）异常率高于MCV。结论NCV及H反射检查对酒精中毒性周围神经病的诊断有参考价值。     

Arsenic exposure to smelter workers. Clinical and neurophysiological studies

Forty-seven copper smelter workers, exposed to airborne arsenic for 8-40 years, were examined clinically with electromyography, and the motor and sensory conduction velocities in their arms and legs were determined. Fifty age-matched industrial workers not exposed to arsenic formed a reference group. The level of arsenic in the air at the smeltery was estimated to be below 500 micrograms/m3 before 1975 and approximately 50 micrograms/m3 thereafter. Urine analyses of arsenic showed a mean value of 71 micrograms/l (1 mumol/l) in the exposed group; this value is lower than that found in earlier studies reporting clinically detectable neuropathy. Only minor neurological and electromyographic abnormalities were found. A slightly reduced nerve conduction velocity in two or more peripheral nerves was more common among the arsenic workers than the referents, and a statistically significant correlation between cumulative exposure to arsenic and reduced nerve conduction velocity in three peripheral motor nerves was found. This occurrence was interpreted as a sign of slight subclinical neuropathy. In conclusion the risk of clinically significant neuropathy is small when exposure is kept below 50 micrograms/m3 in workroom air. The subclinical findings may be of interest in relation to the prevention of early adverse health effects from arsenic exposure.     

Association of arsenic exposure during pregnancy with fetal loss and infant death: a cohort study in Bangladesh

The authors evaluated the effect of arsenic exposure on fetal and infant survival in a cohort of 29,134 pregnancies identified by the health and demographic surveillance system in Matlab, Bangladesh, in 1991-2000. Arsenic exposure, reflected by drinking water history and analysis of arsenic concentrations in tube-well water used by women during pregnancy, was assessed in a separate survey conducted in 2002-2003. Data on vital events, including pregnancy outcome and infant mortality, were collected by monthly surveillance at the household level. The risk of fetal loss and infant death in relation to arsenic exposure was estimated by a Cox proportional hazards model. Drinking tube-well water with more than 50 microg of arsenic per liter during pregnancy significantly increased the risks of fetal loss (relative risk = 1.14, 95% confidence interval: 1.04, 1.25) and infant death (relative risk = 1.17, 95% confidence interval: 1.03, 1.32). There was a significant dose response of arsenic exposure to risk of infant death (p = 0.02). Women of reproductive age should urgently be prioritized for mitigation activities where drinking water is contaminated by arsenic.     

Subclinical cervico-spino-bulbar effects of lead: a study of short-latency somatosensory evoked potentials in workers exposed to lead, zinc, and copper

Subclinical central and peripheral nervous system dysfunction among lead-exposed workers was studied by measuring short-latency somatosensory evoked potentials (SSEP) and maximal motor and sensory nerve conduction velocities (MCV and SCV) following stimulation of the median nerve at the wrist. The examinations were conducted in 20 gun-metal foundry workers exposed to lead, zinc, copper, and tin, with blood lead (BPb) concentrations of 16 to 64 micrograms/dl (mean, 42 micrograms/dl). The interpeak latency of SSEP in the cervico-spino-bulbar region [N9(Erb)-N13 latency] was significantly prolonged, and the MCV and SCV in the forearm were significantly slowed. Multiple regression analysis revealed that the yield of urinary lead following challenge with calcium disodium ethylenediamine tetraacetate (CaEDTA) and packed red blood cell volume were the major factors associated with the prolongation of SSEP latency in the cervico-spino-bulbar region. Similarly, the interpeak latency in the upper central nervous system (N13-N20 latency) was inversely related to the zinc concentration in erythrocytes; latency up to the Erb's point [N9(Erb) latency], which reflects conduction time in a long pathway of the sensory median nerve, was inversely related to urinary zinc level; the MCV and SCV in the palm were positively related to erythrocyte zinc concentration and plasma copper concentration, respectively. These findings suggest that the subclinical neurophysiological effects of lead occur not only in peripheral nerves but also in the central nervous system. It appears that zinc antagonizes the central and peripheral neurologic dysfunction caused by lead; similarly, copper antagonizes the peripheral sensory nerve dysfunction.     

Reversible nerve lesions after accidental polychlorinated biphenyl exposure

Several capacitors containing polychlorinated biphenyls (PCB) exploded in a cardboard plant. During the accident, and in the clearing work, several workers were in probable contact with PCB and/or its degradation products. Nausea, intense perspiration, and headache were acute symptoms, which cleared quickly. The 15 men with the greatest exposure were studied neurophysiologically twice, namely, two and six months after the explosion. Motor conduction velocities (MCV) of the right median, ulnar, and peroneal nerves; sensory conduction velocity (SCV) of the right sural nerve; and distal SCVs of the right median and ulnar nerves were measured with skin electrodes. Thirty male workers with a similar age distribution served as referents. Two months after the explosion all SCVs and distal SCVs were slower in the exposed men, and still six months after the explosion the distal SCV of the ulnar nerve and the SCV of the sural nerve were slightly slower among the exposed. However, clear improvement occurred in the distal SCVs during the follow-up. As in many toxic distal axonopathies, the distal SCVs were reversibly impaired after an accidental exposure to PCB fumes. PCB seem to exhibit neurotoxic properties in humans.     

Effects of lead,zinc and copper absorption on peripheral nerve conduction in metal workers

Summary To examine the antagonistic effects of lead, zinc and copper on the nervous system in man, we measured maximal motor and sensory conduction velocities (MCV and SCV, respectively) in the distal radial and median nerves in 20 gun metal founders with asymptomatically increased absorption of these metals [blood lead concentrations ranged from 16 to 64 g/dl (mean 42)]; and analyzed metal effects on nerve conduction by multiple regression analysis. The MCVs in the radial and median nerves and the SCV in the forearm segment of the median nerve were significantly slowed; indicators of lead absorption (urinary delta-aminolevulinic acid and coproporphyrin) were inversely correlated with the SCV in the radial nerve. The SCVs in the radial nerve and in the hand segment of the median nerve, which were not significantly slowed, were positively related to indicators of copper absorption (plasma or erythrocyte copper). The SCV in the radial nerve was also positively related to the indicator of zinc absorption (plasma zinc); similarly, the MCVs in the radial and median nerves were positively related to the indicators of zinc absorption (erythrocyte or urinary zinc). These findings suggest that copper and zinc antagonize the subclinical effects of lead on peripheral nerve conduction velocities; the conduction velocity in the distal radial nerve is sensitive not only to asymptomatic lead absorption but also to zinc and copper absorption.     

Vascular dysfunction in patients with chronic arsenosis can be reversed by reduction of arsenic exposure

Chronic arsenic exposure causes vascular diseases associated with systematic dysfunction of endogenous nitric oxide. Replacement of heavily arsenic-contaminated drinking water with low-arsenic water is a potential intervention strategy for arsenosis, although the reversibility of arsenic intoxication has not established. In the present study, we examined urinary excretion of cyclic guanosine 3 ,5 -monophosphate (cGMP), a second messenger of the vasoactive effects of nitric oxide, and signs and symptoms for peripheral vascular function in 54 arsenosis patients before and after they were supplied with low-arsenic drinking water in an endemic area of chronic arsenic poisoning in Inner Mongolia, China. The arsenosis patients showed a marked decrease in urinary excretion of cGMP (mean +/- SEM: male, 37.0 +/- 6.1; female, 37.2 +/- 5.4 nmol/mmol creatinine), and a 13-month period of consuming low-arsenic drinking water reversed this trend (male, 68.0 +/- 5.6; female, 70.6 +/- 3.0 nmol/mmol creatinine) and improved peripheral vascular response to cold stress. Our intervention study indicates that peripheral vascular disease in arsenosis patients can be reversed by exposure cessation and has important implications for the public health approach to arsenic exposure.     

神经生长因子治疗铅中毒周围神经病的临床疗效分析

目的分析神经生长因子治疗慢性铅中毒性周围神经病的疗效。方法选取本院2006年12月-2011年6月期间住院治疗的慢性铅中毒性周围神经病患者124例,随机分为治疗组和对照组,对照组予以VitB10.1 mg、VitB12500μg肌肉注射,每日1次,治疗组在前述基础上增加神经生长因子18μg肌肉注射,每日1次,疗程均为8周。结果治疗组的正中神经、尺神经和腓神经的运动和感觉神经传导速度均较治疗前明显增快,与对照组比较,差异有统计学意义（P〈0.01）,且临床症状改善的有效率也比对照组明显（P〈0.01）。结论神经生长因子对慢性铅中毒性周围神经病的治疗是安全有效的方法,值得推广。