北京市0～6岁儿童血铅水平与相关影响因素的研究

目的　了解近期北京市 0～ 6岁儿童血铅水平及其影响因素。方法　采取分层整群随机抽样的方法。 2 0 0 1年 5～ 7月调查北京市常住人口中 0～ 6岁儿童 2 2 62名。采用石墨炉原子吸收法进行微量血中铅含量的测定 ,并做相关因素问卷调查。结果　北京市 0～ 6岁儿童血铅水平均值为96.8μg L,血铅值≥ 10 0 μg L为 3 5.7% ,血铅值≥ 2 0 0 μg L为 2 .5%。农村儿童铅中毒为 43 % ,明显高于城区和郊区儿童。 2岁组铅中毒为 45.1%高于其他年龄组。男童血铅平均值 10 0 .2 μg L明显高于女童血铅平均值 93 .0 μg L(P <0 .0 1)。不喝或偶喝牛奶、居室距繁华马路≤ 50m、家庭居住 1层楼房或平房为儿童高血铅的主要危险因素。结论　目前北京市儿童血铅水平≥ 10 0 μg L的比例不容忽视 ,应对重点人群采取行之有效的干预措施     

Hippocampal NMDA receptor mRNA undergoes subunit specific changes during developmental lead exposure

The N-methyl- -aspartate (NMDA) receptor has shown to play an important role in the cognitive deficits associated with developmental lead (Pb) exposure. In this study, we examined the effects of low-level Pb exposure on NMDA receptor subunit gene expression in the developing rat brain. The pattern of NR1, NR2A, NR2B, and NR2C subunit mRNA in situ hybridization was consistent with previous studies. Brain levels of NR1 and NR2A mRNAs were lowest shortly after birth, increasing to reach peak levels by 14 or 21 days of age and subsequently decreasing at 28 days of age. NR2B mRNA levels were highest during early development and decreased as the animals aged. NR2C subunit mRNA was restricted to the cerebellum and a signal was not detectable until the second week of life. Lead exposure resulted in significant and opposite effects in NR1 and NR2A subunit mRNA expression with no changes in NR2B or NR2C subunit expression. The Pb-induced changes in NR1 and NR2A subunit mRNA were mainly present in the hippocampus. Hippocampal NR1 mRNA levels were significantly increased in the CA1 (15.3%) and CA4 (26.8%) pyramidal cells from 14-day-old Pb-exposed rats. At 21 days of age, only the NR1 mRNA at the CA4 subfield remained significantly elevated (10.3%). Lead exposure caused reductions of NR2A mRNA levels (11.9–19.3%) in the pyramidal and granule cell layers of the hippocampus at 14 and 21 days of age. NR1 mRNA levels were also significantly increased (14.0%) in the cerebellum of 28-day-old rats with no change in NR2A mRNA at any age. No significant changes in subunit mRNA levels were present in cortical or subcortical regions at any age. The Pb-induced changes in hippocampal NMDA receptor subunit mRNA expression measured in the present study may lead to modifications in receptor levels or subtypes and alter the development of defined neuronal connections which require NMDA receptor activation.     

Effects of lead on red blood cell membrane proteins

Summary The effects of lead on red blood cell (RBC) membrane proteins were studied in two groups of workers with different lead exposure levels: Group 1 (6 subjects employed in a battery plant) with a mean blood lead of 40.1 (SD = 3.7) g/100 ml; Group II(5 workers employed in different industries) with a mean blood lead of 60.6 (SD = 8.0) g/100 ml, compared with a control group with mean blood lead of 15.6 (SD = 9.3) g/100 ml. The analysis of RBC membrane polypeptides was carried out by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and by using a densitometer for percentage measurement of the bands corresponding to protein fractions. The results show a very significant decrease in Band 3 (anion channel) and 4.1 in more exposed workers (Group II) only. The effects of lead on RBC membrane proteins seem to be evident at blood-lead levels higher (> 50 g/100 ml) than those previously reported in literature. These results confirm the effects of lead on membrane proteins, even if the exact mechanism, particularly the influence of proteolysis and the meaning of the interference, still needs to be investigated thoroughly.     

The distribution of lead in human hemopoietic tissue and spongy bone after lead poisoning and Ca-EDTA chelation therapy

Two iliac crest needle biopsies were taken from a 43-year-old lead-poisoned woman during and after completion of a Ca-EDTA treatment. By atomic absorption spectroscopy the first and second biopsy were found to contain 56, respectively 41.6 g lead/g wet tissue. In both biopsies 36% of the lead was extractable in 0.1 N HCl. Electron microbeam X-ray analysis proved to have too low sensitivity for quantitation of the lead in these biopsies. Laser microbeam mass analysis (LAMMA), performed only on the second biopsy, revealed a high and fairly constant residual lead concentration in all bone marrow cell nuclei (approximately 55 g/g) and a low lead concentration in the cytoplasm of the same cells (4–12 (g/g). The extracellular bone matrix lead was greatly concentrated in the superficial 3–6 m osteoid zone of the bony trabeculae and totally absent from deeper parts of the mineralized matrix. The LAMMA results are in good agreement with those of subcellular fractionation experiments and atomic absorption spectroscopy, provided that the relative volume fraction of nucleus and cytoplasm is accounted for. The high residual osteoid lead after completed chelation therapy indicates that lead has a stronger affinity for the organic than the mineral components of bone matrix.     

A new HPLC fluorimetric method to monitor urinary delta-aminolevulinic acid (ALA-U) levels in workers exposed to lead

Summary A new sensitive HPLC method for the determination of urinary delta-aminolevulinic acid (ALA-U) was used to evaluate the relationship between blood-lead (Pb-B) and ALA-U levels in male workers exposed to lead. The differences between the ALA-U levels determined by this method (ALAU-HP) and by a colorimetric method (ALA-U-CL) are discussed. The HPLC method gave values similar to the ALA-U-CL values at high ALA-U level. However, at low blood-lead levels (58 ± 22 g/l, n = 23), the mean ALA-U-HP level corrected by urinary creatinine level was one-third of the corrected ALA-UCL level (0.83 ± 0.14 and 2.4 ± 0.5 mg/g creatinine, respectively). A significant increase of the mean corrected ALA-U-HP level was observed at 162 ± 22 g/l Pb-B (P < 0.05, n = 26), while that of ALA-UCL was observed at 245 ± 30 g/l Pb-B (P < 0.01, n = 37). The regression equation based on the logistic model fitted well to the relationship data between the Pb-B level and the percentage of the subjects with corrected ALA-U-HP above the cut-off point (1.12 mg/g creatinine) and the expected Pb-B level for 50% response was 270 g/l Pb-B, while it did not fit well to the relationship data between Pb-B level and the percentage of the subjects with corrected ALAU-CL above the cut-off point (3.5 mg/g creatinine). The maximum responses for the two sets of corrected ALA-U levels were both observed at 625 ± 25 g/l. The corrected ALA-U level by HPLC method seems to be a useful indicator for biological monitoring of exposure to lead at low levels (< 400 g/l Pb-B = health-based biological limit, WHO) as well as high ones.     

Electrode Positioning for Reliable Telemetry ECG Recordings During Social Stress in Unrestrained Rats

We describe a surgical procedure for optimizing the location of telemetry ECG leads in rats. The new location was aimed at obtaining an accurate representation of ECG features throughout the cardiac cycle by limiting the voltage instability usually observed during intense somatomotor activity and improving the signal-to-noise ratio. The two electrodes (wire loops) were fixed on the dorsal surface of the xiphoid process and in the anterior mediastinum close to the right atrium. The implantation procedure was fast, little invasive, and allowed animals to completely recover from intervention. The performance of the “improved” location (IL, n = 10) with respect to two subcutaneous (SC) positionings (“conventional positioning,” CSP, n = 5; “updated location,” USL, n = 5) was evaluated by comparing ECGs obtained in baseline, stress and recovery conditions and during different behavioral activities (immobility and grooming). The resident-intruder test (emotional/physical challenge) was chosen as experimental stress paradigm. The noise level of ECGs obtained from IL rats was lower than in CSP and USL animals, in all recording conditions. Percentages of correctly recognized beats (CRBs) over the total number of beats (TBs) were significantly higher in IL rats than in CSP and USL animals, both in baseline conditions (99% vs. 11% and 40%) and situations involving high somatomotor activity (stress: 97%, 5% and 16%; recovery: 97%, 7%, and 15%) (p < 0.01). The performance of IL as compared to CSP and USL was also better when percentages during grooming and immobility were considered (grooming: 93% vs. 4% and 23%; immobility: 97%, 6%, and 33%; p < 0.01).     

不同导联系统记录体表心室碎裂电位效果对比研究

本文分别应用标准１２导联系统，Ｆｒａｎｋ正交导联系统和改良Ｆｒａｎｋ正交导联系统记录健康人３６例、陈旧性心肌梗塞４２例的心室碎裂电位，通过分析这些导联系统中相互垂直或近似垂直的导联上ＶＦＰ的形态，数量关系，发现改良Ｆｒａｎｋ正导联系统记录ＶＦＰ较其它导联系统更科学，合理，且操作方便。     

The pathogenesis of lead encephalopathy

Summary The toxic effects of inorganic lead feedings on the immature brain were studied in the rat pup. Beginning when litters were two weeks old, PbCO₃ was fed to nursing mothers and then to pups directly after weaning. Results in lead-fed pups were compared to age-matched controls and to lead-fed young adult males (60 days old). Anaemia and growth failure developed in both pups and adults. In the second week, more than half the pups developed an encephalopathy, with haemorrhage and oedema predominately in the cerebellum and lead-containing densities in the cerebellar molecular layer. The latter were confirmed by X-ray microanalysis. No lead-fed adults showed signs of an encephalopathy.Cerebellar mitochondria from lead-fed pups, studied polarographically, showed a very early loss of respiratory control and a subsequent inhibition of phosphorylation-coupled respiration with NAD-linked substrates but not with succinate. Compared to the pup cerebellum, these changes were much less marked in immature cerebral mitochondria and were not found in adult cerebral or cerebellar mitochondria.Cerebral and cerebellar homogenates from immature and mature lead-fed animals showed large increases in lead content measured by atomic absorption spectrophotometry. Immature cerebellar mitochondrial lead contents were increased to the same extent as in the homogenates. Mitochondria from immature cerebrum and from both regions in the mature brain showed less immediate and smaller increases in lead content.In conclusion, altered mitochondrial respiration occurs early in regional and age-dependent association with lead encephalopathy in the rat pup. The development of lead encephalopathy also is associated with increased mitochondrial lead concentrations.     

Investigations on neurotoxicity of chemical substances at the workplace

Summary A cross-sectional study was performed in order to investigate the influence of chronic lead-exposure on the peripheral nervous system. We examined 148 male workers of a storage battery manufacturing plant, who had been exposed to lead metal and inorganic lead compounds for 1 to 28 years (mean 11 years). Fifteen workers with non-occupational risks of peripheral neuropathy (former diseases, alcohol abuse, medication) were excluded from the study. The investigation program comprised: case history, physical examination, analyses of blood- and urine-samples and determination of maximal motor, mixed and sensory conduction velocity (NCV) of the ulnar and median nerve of the right forearm. Objectively no worker showed any signs of health effects related to lead exposure. The Biological Monitoring included the determination of (1) Blood-lead level (Pb-B), (2) Free erythrocyte porphyrins (FEP), (3) -Aminolevulinic acid dehydratase (ALA-D) and (4) -Aminolevulinic acid in urine (ALA-U). Further time-weighted-average (TWA)-values of Pb-B were calculated on the basis of several determinations over the period 1975–1981. The following actual (TWA) median values resulted: Pb-B 53 g/dl (54 g/dl), ALA-U 5.6 mg/l (8.4 mg/l), FEP 2.0 mg/l (2.0 mg/l). The Biologischer Arbeitsstoff Toleranz Wert (BAT) of 70 g//dl for Pb-B was exceeded in 15 workers (11%), and of 15 mg/l for ALA-U in 30 cases (23%). In comparison with age-matched controls, the lead workers showed a mild slowing of NCV with mean values between 0.8 and 2.0 m/s. Multiple stepwise regression analyses revealed statistically significant correlations between the four NCV and age as well as Pb-B. There were better correlations by using TWA than actual data of Pb-B. Consideration of the results of the regression analyses, together with an evaluation of the individual neurophysiological status as a function of internal lead exposure, a dose-effect-relationship was found only in the case of Pb-B exceeding 70 g/dl. From our study it is concluded that chronic lead exposure resulting in blood-lead levels of below 70 g/dl is no occupational risk causing a functionally significant slowing of nerve conduction velocities.With Grants from the Deutsche Forschungsgemeinschaft, Bonn (Project no. Va 23/19-1)     

中国9个长寿地区65岁及以上人群血铅浓度与认知功能受损的关联研究

目的探讨65岁及以上人群血铅水平与认知功能受损的关联。方法研究对象来自2017-2018年在我国9个长寿地区开展的“老年健康生物标志物队列研究”,最终将1684名血铅和认知功能数据完整的65岁及以上人群纳入本研究。通过问卷调查和体格检测,收集调查对象的人口学特征、生活方式、健康状况及认知功能评分等信息;同时采集调查对象的静脉血以检测血铅水平。根据血铅水平的四分位数将调查对象分为4组(Q₁-Q₄组),采用多因素logistic回归模型分析血铅浓度与认知功能受损的关系,采用限制性三次样条检验血铅浓度与认知受损之间是否存在非线性关联。结果1684名研究对象年龄为(83.1±11.1)岁,其中女性843名(50.1%);认知功能受损者191名(11.3%)。调整相关混杂因素后,老年人血铅浓度每升高10μg/L,认知功能受损患病风险OR(95%CI)值为1.05(1.01~1.10);与血铅浓度Q1组老年人相比,血铅浓度较高者认知功能受损的患病风险较高,Q₂,Q₃,Q₄组的OR(95%CI)值分别为1.19(0.69~2.05)、1.45(0.84~2.51)和1.92(1.13~3.27)。结论我国9个长寿地区65岁及以上老年人血铅水平与认知功能受损患病风险存在关联。