Early Response of the Canine Respiratory Tract Following Long-Term Exposure to a Sulfur(IV) Aerosol at Low Concentration. IV. Respiratory Lung Function

Abstract

Respiratory function was studied in eight beagle dogs at the end of a 290-day exposure to a sulfur(IV) aerosol [0.3 mg m^?3 S(IV)]and compared to lung function parameters in three dogs exposed to clean air during the same period. The lung mechanics were characterized by lung volumes and quasistatic and dynamic compliances of lungs and thorax. Gas exchange and gas transport were estimated by carbon monoxide rebreathing, single-breath and multiple-breath inert gas washout, and the study of aerosol bolus dispersion. We found a significant decrease in specific lung compliance (728 ± 8 vs. 149 ± 9 ml hPa^?1 p<.05) and a tendency toward a fall in membrane diffusing capacity (21.5 ± 2.7 vs. 25.7 ± 4.3 ml min^?1 hPa ^?1) in S(IV)-exposed dogs. The change in membrane diffusing capacity correlated with a decrease in alveolar surface area as demonstrated by postmortem morphometric analysis flakenaka et al., 1992). No differences were observed between exposed dogs and controls in any of the other parameters of lung function. The results show that chronic inhalation of low levels of S(IV) aerosol induces minor changes in respiratory function.     

Exposure to Inorganic Arsenic Metabolites during Early Human Development

Because of the lack of data on the exposure to and toxic effectsof inorganic arsenic during early human development, the transferof arsenic to the fetus and suckling infant was studied in anative Andean population, living in the village San Antoniode los Cobres in the North west of Argentina, where the drinkingwater contains about 200 µg/liter. The concentration ofarsenic in cord blood (median, 9 µg/liter) was almostas high as in maternal blood (median, 11 µg/liter), andthere was a significant correlation between the two. Thus, atleast in late gestation, arsenic is easily transferred to thefetus. The median concentration of arsenic in the placenta was34 µg/kg, compared with 7 µg/kg previously reportedfor nonexposed women. Interestingly, essentially all arsenicin the blood plasma of both the newboms and their mothers wasin the form of dimethylarsinic acid (DMA), the end product ofinorganic arsenic metabolism. Similarly, about 90% of the arsenicin the urine of both the newboms and mothers in late gestationwas present as DMA, compared with about 70% in nonpregnant women(p < 0.001). This may indicate that methylation of arsenicis increased during pregnancy and that DMA is the major formof arsenic transferred to the fetus. The increased methylationin late gestation was associated with lower arsenic concentrationsin blood and higher concentrations in urine, compared with afew months postpartum. The arsenic concentrations in the urineof the infants decreased from about 80 µg/liter duringthe first 2 days of life to less than 30 µg/liter at 4.4months (p = 0.025). This could be explained by the low concentrationsof arsenic in the breast milk, about 3 µg/kg.     

Interindividual Differences in Hair Uptake of Air Nicotine and Significance of Cigarette Counting for Estimation of Environmental Tobacco Smoke Exposure

Abstract: Hair from 80 male subjects, smokers and non-smokers, was exposed continously in a dynamic exposure chamber to constant nicotine vapour concentrations of 20, 200 or 2000 μg/m³ for 72 hr. Subgroups of high and low nicotine adsorbing hair were also exposed intermittantly to environmental tobacco smoke for 8 months. Air and hair concentrations of nicotine were determined by gas chromatography/mass spectrometry. The chamber experiments demonstrated a hair nicotine uptake which followed a second order relation to the applied concentrations of nicotine, y=–0.00018x²+0.715x+1.13, r²=0.99999. The function and the experimental points showed linearity up to an air nicotine vapour concentration of about 200 μg/m³ covering the most relevant range of environmental exposure. An approximately 7- and 2-fold interindividual variation was observed in the hair uptake rate constant of nicotine vapour for the investigated material within the 10 to 90 and 25 to 75% percentiles, respectively. The factors causing this variation were not identified. It was shown that subject age, hair diameter and hair content of eumelanin were without correlation to the rate constants of hair nicotine uptake. The exposure of subgroups of hair to environmental tobacco smoke showed similar uptake profiles of nicotine as that experienced with exposure to pure nicotine vapour, supporting the relevance of controlled chamber nicotine vapour exposures as a relevant tool for the evaluation of hair nicotine uptake from a more complex environmental situation. Standardized measurements of air nicotine vapour and particulate concentrations in a modern office during 8 hr periodical smoking periods, showed that the number of cigarettes smoked was a poor indicator for the estimation of individual exposure to environmental tobacco smoke constituents. Hair nicotine measurements so far seem to be superior to other suggested methodologies for estimation of environmental tobacco smoke exposure, but further studies should be initiated to identify factors determining the rate constant of hair nicotine uptake.     

高效液相色谱测定人体血清中低浓度盐酸伪麻黄碱的含量

目的:建立一种测定人体血清中低浓度盐酸伪麻黄碱含量的高效液相色谱法。方法:取人体血清0.5mL,加入内标苯丙醇胺后,加入混合碱溶液(1000mL 水中含有10g 氢氧化钠和40g 碳酸钠)0.5mL 碱化,乙醚-正己烷(1∶1)振荡萃取,离心,有机相盐酸酸化,水浴中氮气挥干。残渣用100μL 流动相溶解,进样。流动相为0.05mol·L~(-1)磷酸二氢钾(含0.005mol·L~(-1)庚烷磺酸钠,用磷酸调pH=2.6)-乙腈(85∶15)。流速:0.8mL·min~(-1)。紫外检测波长:195nm。结果:盐酸伪麻黄碱的线性范围为400-12.5ng·mL~(-1),加权回归r=0.998,最低检测限为8ng·mL~(-1),方法的回收率为60%-80%,日内 RSD 为3.3%-17.5%,日间 RSD 为8.2%-17.8%。结论:本方法灵敏度较文献报道的灵敏度高近10倍,操作简单,专属性和重现性均符合要求,可用于口服低剂量盐酸伪麻黄碱的血药浓度测定和药代动力学研究。     

A Controlled Inhalation Diesel Exhaust Exposure Facility with Dynamic Feedback Control of PM Concentration

A facility has been assembled that provides a controlled inhalation exposure to freshly diluted and mixed diesel exhaust using a diesel engine under load and a two-stage exhaust dilution system with dynamic feedback control. The concentrations of particulate matter less than 2.5 μ m in diameter (PM_2.5), particulate carbon, and gaseous pollutants including carbon monoxide and oxides of nitrogen (NO_x) have been characterized and the exposure conditions have been found to be both stable and reproducible. Control of the PM_2.5 concentration at intended levels relies on the relatively linear relationship between particle light scattering and exhaust particle mass concentration. While the exposure system does not entirely replicate diesel exhaust conditions in the atmosphere due to the relatively low ratio of nitrogen dioxide to total NO_x, the fine particulate matter size distributions are quite similar to those of aged diesel exhaust. The facility enables study of the relationship between diesel exhaust and cardiovascular and respiratory health effects in human and animal models.     

吸入麻醉剂浓度及作用时间对人离体精子活率的影响

目的:研究吸入麻醉剂浓度及作用时间对人离体精子活率的影响。方法:选择人精液20份,上游法优化处理后随机分为异氟醚实验组和七氟醚实验组,各10份。分别观测5个时间点(0.5 h、1 h、2 h3、h4、h)及5个浓度水平(0、1.4%、2.8%、4.2%、5.6%)异氟醚和相似浓度七氟醚对精子活率的影响,精子运动功能采用计算机辅助精子分析系统分析。结果:1.4%~5.6%异氟醚作用于精子0.5~4 h后,精子活率显著升高,其变化趋势符合S型曲线,相同浓度异氟醚组,精子活率随放置时间的延长成直线下降。类似浓度七氟醚对精子活率无显著影响。结论:临床浓度异氟醚作用于人离体精子,可以显著升高精子活率。类似浓度七氟醚对精子活率无显著影响。     

Quantitative Relationship between Phytochelatin Accumulation and Growth Inhibition during Prolonged Exposure to Cadmium in Silene vulgaris

Phytochelatins (PCs) are known to detoxify heavy metals in plants. This study aimed to investigate the possibility of using PCs as a biomarker for chronic Cd toxicity in Silene vulgaris. For this purpose, the effects of Cd on growth rate, related to plant weight, and the PC concentrations were recorded throughout the bigger part of the vegetative phase. The lowest concentrations of Cd used, 1 and 2 M, inhibited plant growth rates by 30 and 50%, respectively, independent of the weight of the exposed plants. Above an exposure concentration of 2 M Cd, the toxic effect increased with plant weight. At 3.5 M Cd, the plant growth rates were inhibited up to 90%. Further increases of the exposure concentration did not produce additional inhibition. Root PC concentrations correlated with growth inhibition only at the lower Cd concentrations, i.e. up to 2 M Cd. Above this concentration the correlation was lost.     

Dermal Exposure to a Compounded Pain Cream Resulting in Severely Elevated Clonidine Concentration

Introduction

Clonidine is an imidazoline derivative antihypertensive medication that is also used as adjunctive therapy for neuropathic pain disorders via topical administration. Clonidine overdose can manifest both central and peripheral alpha-adrenergic agonist effects.

Case Report

A 23-year-old man presented to an emergency department with altered mental status, bradycardia, and hypertension after suspected overdose. He had rubbed a specially compounded medicinal cream over his entire body containing clonidine 0.2 % (w/w), gabapentin 6 %, imipramine 3 %, ketamine 10 %, lidocaine 2 %, and mefenamic acid 1 %. The patient presented with severe hypertension, bradycardia, and altered mental status. He was found to have a subarachnoid hemorrhage and was treated for hypertensive emergency. Toxicological analysis of initial blood samples revealed a serum clonidine concentration of 5,200 ng/ml. At 6-month follow-up, the patient had made a full recovery.

Discussion

There are limited reports of topical clonidine toxicity, and to our knowledge, this case involves the highest concentration yet reported following clonidine overdose by any route of exposure. The severely elevated serum clonidine concentration found in our patient demonstrates the possibility of toxicity resulting from inappropriate use of such a product. At high serum concentrations, the pharmacodynamic effects of clonidine appear to cause significant peripheral alpha-1 adrenergic stimulation. Toxicologists should be aware of the increasing use of topical clonidine preparations for the treatment of neuropathic pain and the potential for toxicity.     

毛发中大麻类物质的检测

目的对毛发中大麻类物质的检测方法进行综述。方法参考国内外近期的有关文献,介绍了毛发中大麻类物质分析的基本理论及发展概况,从毛发样品的采集、预处理、分析方法、优势和不足等几方面概述了毛发分析的过程。结果毛发作为生物检材具有不易造假,可反映药物长期滥用的情况等特点。结论毛发作为生物检材具有广泛的应用前景。     

Long-Term Sequelae of Soman Exposure: Hormonal Rhythms Two Weeks Postexposure to a Single Dose

Long-Term Sequelae of Soman Exposure: Hormonal Rhythms Two WeeksPostexposure to a Single Dose. KANT, G. J., SHIH, T.-M., LEU,J. R., RASLEAR, T. G., AND MOUGEY, E. H. (1988). Fundam. ApplToxwol. 10, 154–163. Two weeks following a single exposureto either soman (100 µg/kg, sc) or saline, rats were sacrificedat 2-hr intervals over a 26-hr period. Trunk blood was collectedand plasma was stored until assayed for corticosterone, prolactin,growth hormone, adrenocorticotropin, -endorphin, and ß-lipotropin.Rats surviving for 2 weeks following soman appeared well groomedand were gaining weight at a rate similar to saline-treatedrats at the time of termination. Thus, they appeared to haverecovered from the initial physiological effects of soman exposure.However, substantial differences in plasma levels of most hormoneswere seen in comparing soman- vs saline-treated rats. Levelsof prolactin were suppressed at all time points in soman-treatedrats. Growth hormone secretion was also suppressed and the normalepisodic peaks of growth hormone were missing in soman-treatedrats. Both soman- and saline-treated rats displayed circadianrhythms in levels of plasma corticosterone, but the usual lateafternoon rise in plasma corticosterone levels was shifted toearlier time points in the soman-treated rats. Levels of ß-endorphinand ß-LPH were slightly but significantly suppressedin so-man-treated rats at almost all time points. Levels ofadrenocorticotropin were similar in control and soman-treatedrats. The results of this experiment demonstrate that a singleexposure to soman may have long-lasting effects on neuroendocrinefunction.     

Sensory,Symptomatic, Inflammatory,and Ocular Responses to and the Metabolism of Methyl Tertiary Butyl Ether in a Controlled Human Exposure Experiment

Abstract

The Clean Air Act of 1990 mandates that those areas of the country that do not attain the health-based National Ambient Air Quality Standard for CO must add oxygenates (2.7% by weight) to auto fuels (oxyfuels). In the fall of 1992, the addition of methyl tertiary butyl ether (MTBE) to automotive fuels coincided with complaints of illness in some parts of the country. In Alaska, the reported symptoms included headache, nasal, throat, or ocular irritation, nausea or vomiting, dizziness, and sensations of “spaciness” or disorientation. We conducted a chamber exposure experiment to determine if exposure to pure MTBE would elicit similar responses to those reported to be related to MTBE exposure. Nineteen male and 18 female subjects were exposed in a repeated-measures design to clean air (CA) and 1.39 ppm (5.0 mg/m³) MTBE for 1 h. This level was selected to approximate a typical exposure experienced during refueling. Exposures were separated by at least I wk. Symptom questionnaires were completed before and during exposure. Cognitive testing was completed once during exposure. Objective measures of ocular and nasal irritation were obtained pre- and postexposure. Four questions relevant to the reported symptoms, relating to air quality, odor strength, headache, and nasal irritation, were considered confirmatory hypotheses. All other measures were exploratory. The only significant confirmatory result was a difference in rating of CA quality by the female subjects as better than during the MTBE exposure. No other measures, objective or cognitive, approached significance. These results indicate that in young, healthy subjects a 1-h exposure to 1.39 ppm MTBE does not increase symptom reporting or result in increases in objective biomarkers of inflammation. Two subjects also participated in a study of the pharmacokinetics of MTBE in which blood samples were obtained before, during, and at various time points up to 7 h postexposure. MTBE in blood rose rapidly and was metabolized to tertiary butyl alcohol (TBA), which gradually increased in the blood and maintained an elevated level for the duration of the sampling.     

反向离子对高效液相色谱法测定人血浆中尼古丁浓度

目的建立一种简便、准确的高效液相色谱法测定人血浆中尼古丁浓度。方法采用反向离子对高效液相色谱法,Kromasil C18色谱柱（250mm×4.6mm,5μm）,缓冲液（30mmol.L-1磷酸二氢钠,30mmol.L-1柠檬酸三钠,4mmol.L-1辛烷磺酸钠,pH 4.5）-乙腈（85∶15）,流速1.0mL.min-1,紫外检测波长260nm,柱温35℃,以2-苯基咪唑为内标。结果尼古丁在0.04～2.56mg.L-1范围内线形关系良好,标准曲线为Y=0.0009X-0.007,r=0.99995,相对回收率95.2～106.36%,提取回收率67.5～77.3%,日内RSD≤3.1%,日间RSD≤6.8%。血样在-20℃下保存30d后尼古丁含量无明显降低。结论本法具有灵敏度高、准确性好、色谱峰分离良好等特点,适用于人血浆样本中尼古丁浓度的测定。     

Long-Term Respiratory Disorders of Claimers with Subclinical Exposure to Chemical Warfare Agents

It is well documented that inhalation of sulfur mustard causes injury of the respiratory system. While all of the reports and surveys thoroughly document long-term pulmonary effects after significant exposure to mustard, there is no direct evidence that addresses the issue of long-term respiratory effects in individuals who were exposed to very low level of mustard and suffered no acute respiratory tract injury. Our subjects were selected among all those who were in chemically contaminated areas with chemical warfare agents (CWA) and had been registered for an annual checkup. Subclinical exposure's definition is the absence of any acute symptoms at the time of exposure. We used standard respiratory questionnaires, and chest HRCT examinations and a pulmonary function test were done. Based on exclusion criteria from total of 200 patients claiming respiratory problems, just 77 veterans entered the study. After performing HRCT for all our patients there were 13 (38.23%) veterans with no observable defect, 13 (38%) of them had just significant air trapping in their HRCTs. All the others had at least air trapping (AT), which added to other defects. Septal wall thickening was seen in five veterans (14.7%) and bronchiectasis was seen in three (8.8%) cases. This study suggest that exposure to CWA was responsible for the occurrence of the bronchiolitis obliterans syndrome observed in our patients. There are many civilian and military people who have been present in contaminated area without signs and symptoms at the time of exposure, and early detection of such a population could be lifesaving.     

Human Performance and Physiological Function during a 24-hr Exposure to 1% Bromotrifluoromethane (Halon 1301)

Performance and physiological measurements were obtained fromfour pairs of men exposed for 24 hr to 1% (10,000 ppm) Halon1301 (bromotrifluoromethane, CBrF₃) and to air with order counterbalancedusing a double-blind protocol. Cognitive and motor performancewas assessed before, during, and after the exposures using sevenscales of the Automated Portable Testing System, which produced13 measures of performance. Halon inhalation induced decrementsin 2 of the 13 measures, but actual and estimated magnitudesof the decrements were no greater than 5% of baseline values.Physiological data were obtained before, during, and after theexposures from clinical chemistry analyses of blood and urinesamples, pulmonary function tests, and monitoring of vital signs.Significant change during Halon inhalation was observed for6 of the 52 variables assessed; however, all physiological valuesremained within clinically acceptable limits. No cardiovasculareffects were noted. This study demonstrated that exposure to1% Halon 1301 for 24 hr can produce minor disturbance of centralnervous system function as assessed by cognitive tasks.     

Long-Term Pulmonary Histopathologic Changes in Rats Following Acute Experimental Exposure to Chlorine Gas

In this study, we aimed to investigate the long-term histopathologic changes in the lungs of rats exposed to a high concentration of chlorine gas. Twenty-four Sprague-Dawley rats were divided into three groups: the control group (group I) (n = 8), early-examined group (group II) (n = 8), and late-examined group (group III) (n = 8). In group II the lungs of rats were taken out just after the exposure, whereas in group III the lungs were taken out 45 days after the exposure. Eosinophilic liquid accumulation in alveoli and bronchi, diffuse intraalveolar edema, vascular congestion, severe perivascular edema, and free bleeding in intraalveolar and interstitial area were observed in the lungs of rats in group II. Interstitial fibrosis and thickening of the alveolar septa were observed in group III. These findings suggest that the people using these cleaning agents are at risk of harming themselves, and the victims of chlorine gas injury should be reexamined at a later period since they may have pulmonary damage even after 45 days of exposure.     

Controlled Cell Death by Magnetic Hyperthermia: Effects of Exposure Time,Field Amplitude,and Nanoparticle Concentration

Purpose  

To investigate the effects of alternating magnetic fields (AMF) on the death rate of dendritic cells (DCs) loaded with magnetic nanoparticles (MNPs) as heating agents. AMF exposure time and amplitude as well as the MNPs concentration were screened to assess the best conditions for a controlled field-induced cell death.     

Reward Sensitization: Effects of Repeated Nicotine Exposure and Withdrawal in Mice

Tobacco dependence is an addiction with high rates of relapse, resulting in multiple quit attempts in individuals who are trying to stop smoking. How these multiple cycles of smoking and withdrawal contribute to nicotine dependence, long-term alterations in brain reward systems, and nicotine receptor regulation is unknown. Therefore, to evaluate how multiple exposures of nicotine and withdrawal periods modulate rewarding properties of nicotine, we used intracranial self-stimulation to measure alterations in the threshold of brain stimulation reward. In addition, we employed the conditioned place preference (CPP) paradigm to evaluate positive context conditioning following each withdrawal period and measured levels of neuronal nicotinic receptors in cortex, striatum, and hippocampus. We found that repeated nicotine exposure and withdrawal enhanced brain stimulation reward and reward sensitivity to acute injections of nicotine. This increased reward was reflected by enhanced CPP to nicotine. Chronic nicotine is known to up-regulate nAChRs (nicotinic acetylcholine receptors) and we found that this up-regulation was maintained for up to 8 days of withdrawal in the striatum and in the hippocampus, but not in the cortex, of animals exposed to multiple nicotine exposure and withdrawal periods. These results demonstrate that repeated exposures to nicotine, followed by withdrawal, induce a persistent increase in both brain reward function and sensitivity to the hedonic value of nicotine and long-lasting up-regulation of neuronal nicotinic receptors. Together, these data suggest that a continuing increase in brain reward function and enhanced sensitivity to nicotine reward following repeated withdrawal periods may be one reason why smokers relapse frequently.     

Lipid Peroxidation in Rats Subacutely Exposed to a Low Concentration of Aerosolized Cadmium Chloride

Abstract

Lipid peroxidation (LPO) was evaluated at 1, 5, 10, 15, and 45 days in the lungs, liver, and kidneys of rats exposed to a low concentration of aerosolized cadmium chloride (50 μg Cd/m³ as CdCl₂ MMAD 0.3 µm; σ_g - 1.3) during 4 h/day for 14 days. Results demonstrate that LPO was significantly increased in lung tissue 24 h aher the first exposure (178%; p ≤ .01), while activities of the antioxidant defense components, namely, glutathione peroxidase (GPX), glutathione reductase (GR), and superoxide dis-mutase (SOD), were not affected. On the other hand, activity of glucose-6-phosphate dehydrogenase (G6PDH) was significantly increased at day 1. Subsequent exposures had no effect on lung LPO but produced significant changes in GR and G6PDH, while CPX and SOD remained unchanged. These various parameters were not significantly altered in liver and kidneys. The results reported in the present study demonstrate that LPO is an early response of the lung tissue following inhalation of low concentrations of CdCl₂ They also suggest that alterations of the antioxidant defense system are not responsible for the stimulation of the LPO reaction.