中和抗体对促黄体激素释放激素-绿脓杆菌外毒素A暴露水平的影响

目的研究恒河猴注射促黄体激素释放激素-绿脓杆菌外毒素A(GP38)后体内中和抗体的产生及其对药物暴露水平的影响。方法恒河猴24只随机分成4组(即对照组、低、中、高剂量组),每组6只,♀♂各半,分别给予生理盐水、50、100、300μg.kg-1GP38;采用ELISA法测定GP38及抗体滴度,中和抗体的测定采用IC50法间接测定。结果恒河猴给药2 wk后产生抗体,具有中和GP38活性的作用;GP38首次静脉注射50、100、300μg.kg-1时,毒代动力学参数Cmax分别为(866±88)、(1466±113)、(5436±733)μg.L-1,AUC0-t分别为(322±33)、(587±93)、(2201±307)μg.h.L-1,MRT分别为(0.27±0.02)、(0.31±0.02)、(0.40±0.08)h;相同剂量反复给药,第7次(d 14)给药后的毒代动力学参数Cmax分别为(352±136)、(589±372)、(1013±642)μg.L-1,AUC0-t分别为(139±55、322±222)、(962±743)μg.h.L-1,MRT分别为(0.26±0.03)、(0.39±0.08)、(0.68±0.45)h;试验动物毒性反应在给药1～3 wk较严重,之后毒性反应逐渐减弱。结论恒河猴反复静脉注射GP38,能够产生中和抗体,降低药物的体内暴露水平。     

Brominated Flame Retardants in Fish of Lake Geneva (Switzerland)

Polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecane (HBCD) were determined in fish (Salmo trutta forma lacustris) from Lake Geneva. Brominated flame retardants were detected in all nine samples with an average concentration for the sum of BDE-28, BDE-47, BDE-49, BDE-66, BDE-99, BDE-100, BDE-119, BDE-153, BDE-154 and BDE-209 of 207 ng per g lipid weight (ng g lw⁻¹). The congener patterns were dominated by BDE-47. The average concentration of HBCD was 168 ng g lw⁻¹.     

Composition,Distribution, and Characterization of Polybrominated Diphenyl Ethers in Sandstorm Depositions in Beijing,China

This study was conducted to determine the concentration of 8 polybrominated diphenyl ethers (PBDEs) in sandstorm depositions in Beijing, China. The PBDE concentrations in 10 samples collected in Beijing ranged from 8.47 to 29.02 ng g⁻¹, with BDE-209 as the predominant congener (>85%). Principal component analysis revealed that the major source of PBDEs in Beijing may be potentially associated with deca-BDE. Furthermore, increasing PBDE contamination was observed from northwest to east Beijing. Finally, possible factors affecting contamination of the sandstorm depositions were subsequently explored revealing a significant correlation between ΣPBDEs and the minimum particle size of the sandstorm deposition samples.     

Protective effect of N-acetylcysteine against BDE-209-induced neurotoxicity in primary cultured neonatal rat hippocampal neurons in vitro

Globally, brominated diphenyl ether-209 (BDE-209) is the most widely used polybrominated diphenyl ether (PBDEs). It has been reported that BDE-209 induces developmental neurotoxicity in vivo. The purpose of this study was to use an antioxidant, N-acetylcysteine (NAC), as an antidote for the neurotoxic effect of BDE-209. We used primary hippocampal neurons from rats for the in vitro cultures. BDE-209 was added to the cultures in increasing concentrations and co-cultured with NAC in order to assess the effect of NAC on BDE-209-induced neurotoxicity. We measured cell viability, apoptosis, expression of phosphorylated p38 mitogen-activated protein kinases (MAPK), intracellular calcium content, and intracellular reactive oxygen species (ROS) levels. The difference between the BDE-209 groups without NAC and the blank control groups was significant (P < 0.05). The difference between the NAC treatment groups and the BDE-209 groups without NAC was also significant (P < 0.05), showing that BDE-209 increased apoptosis, the expression of p38 MAPK, the calcium ion concentration, and the ROS level and decreased cell viability. In contrast, NAC reduced the degree of cellular cytotoxicity induced by BDE-209. The results suggested that NAC may be able to attenuate BDE-209-induced neurotoxicity.     

Studies on the carbodiimide-mediated model couplings of Z-Pro-Leu-OH with benzoaza-15-crown-5

A series of model DCC-mediated couplings of Z-Pro-D-Leu-OH with 2,3-benzo-10-aza-1,4,7,13-tetraoxacyclopentadeca-2-ene were studied by high-performance liquid chromatography. It was found that racemization during preparation of N-(Z-Pro-Leu-)benzoaza-15-crown-5 is promoted by HOBT, an additive usually reducing this process.     

Plasma concentrations of selected organobromine compounds and polychlorinated biphenyls in postmenopausal women of Québec, Canada

BACKGROUND: Brominated flame retardants, especially polybrominated diphenyl ethers (PBDEs), have been widely used in North America, but little is known about the level of exposure of human populations to these compounds. OBJECTIVES: We set out to assess the internal exposure of postmenopausal Canadian women to selected organobromine compounds and to investigate factors associated with this exposure. METHODS: We measured concentrations of four PBDEs, one polybrominated biphenyl, and for comparative purposes, 41 polychlorinated biphenyl (PCB) congeners in plasma samples from 110 healthy postmenopausal women who were recruited at a mammography clinic in 2003-2004. RESULTS: PBDE-47 was the major PBDE congener, with a mean (geometric) concentration of 8.1 ng/g lipids and extreme values reaching 1,780 ng/g. By comparison, the mean concentration of the major PCB congener (PCB-153) was 41.7 ng/g and the highest value was 177 ng/g. PBDEs 47, 99, and 100 were strongly intercorrelated, but weaker correlations were noted with PBDE-153. As the sum of PBDEs (summation operatorPBDEs) increased, the relative contribution of PBDE-47 to the summation operatorPBDEs increased, whereas that of PBDE-153 decreased. PBDE-153 was the only brominated compound correlated to PCB-153. PBDE levels were not linked to any sociodemographic, anthropometric, reproductive, or lifestyle variables documented in the present study. Age and body mass index gain since the age of 18 years were significant predictors of PCB-153 plasma levels. CONCLUSION: Our results suggest that exposure to PBDE-47 likely occurs through direct contact with the penta-PBDE formulation, whereas exposure to PBDE-153 may originate in part from the food chain.     

Correlation between urinary methoxyacetic acid and exposure of ethylene glycol dimethyl ether in a lithium battery plant

Objective To examine the correlation between airborne ethylene glycol dimethyl ether (EGdiME) exposures and the urinary methoxyacetic acid (MAA) and to approach the issue of a permissible exposure limit for EGdiME. Methods The survey was conducted on Thursday. Workers occupationally exposed to EGdiME, as well as nonexposed controls, were studied in combination with one of the authors, who was coincidentally exposed to EGdiME while carrying out the study. Air levels of EGdiME were determined by personal sampling on passive gas tubes. Urine was collected from nine control subjects and ten workers immediately before and after the shift, and from one of the authors at intervals during 12 h. The analyses of EGdiME in air and MAA in urine were performed by gas chromatography with flame ionization detection. Results The time-weighted average (TWA) air levels of EGdiME ranged from 0.7 to 10.5 ppm during 8 h work shifts. The urinary levels of MAA in one of the authors increased continuously during exposure and after the end of exposure. The levels of urinary MAA in the exposed workers were significantly higher than those in the control subjects. On the other hand, the postshift values were higher than the preshift values in the exposed workers, but the difference was not significant. A linear correlation was found between the TWA air levels of EGdiME and creatinine-adjusted MAA levels in urine collected at the end of the shift (r = 0.933; P < 0.0001). According to our equation, a linear extrapolation to the biological limit value recommended by Shih et al. (1999) of 40 mg MAA/g crea indicated an average inhalation exposure to EGdiME over the workweek of 12 ppm. Conclusions These results indicate that the determination of MAA in urine is suitable for use in the biological monitoring of EGdiME exposure.     

Time trends and individual characteristics associated with polybrominated diphenyl ethers in breast milk samples 2006-2009 in Lower Saxony, Germany

Background

Since 2006 polybrominated diphenyl ether (PBDE) concentrations have been analyzed within the scope of the breast milk project conducted by the Governmental Institute of Public Health of Lower Saxony.

Objectives

Temporal trends and regional distributions of the resident population as well as the relevance of individual factors influencing PBDE concentration were to be determined.

Methods

Four PBDE congeners (BDE-47, BDE-153, BDE-99, BDE-100) have been analyzed. The concentrations are fitted by linear regression models, whereby individual factors of the mother are surveyed by a standardized questionnaire.

Results

A total of 2173 samples taken between 2006 and 2009 shows an estimated total PBDE mean value of 1.68 ng/g lipid weight (l.w.). In contrast to most other studies, the proportion of BDE-153 exceeds the one of BDE-47 (median: 0.51 ng/g l.w. vs. 0.31 ng/g l.w.).BMI shows a positive correlation with BDE-47 and a negative correlation with BDE-153, both statistically significant (p < 0.001). For BDE-153, other significant factors (former breast feeding periods, birth year of the mother and country of birth) reflect also dilution effects and the time of accumulation. A decreasing temporal trend is observed for BDE-47 but not for BDE-153.

Conclusions

The correlation patterns, the temporal trends and the various influencing factors may reflect differences in exposure sources and/or metabolism between the major congeners BDE-47 and BDE-153. Therefore it seems to be necessary to discuss the concentrations of BDE-47 and BDE-153 separately as leading indicators instead of using a total PBDE.     

重型肝炎TGF-α、TNF-α、IL-1β改变的初步研究

研究重型肝炎病程中TGF-α、TNF-α、IL-1β的改变。23例进入研究,用放免法集中检测血清标本。急性期的三种细胞因子均显著高于正常对照(P<0.001)。恢复的TGF-α高于急性期(P=0.092)。TNF-α、IL-1β升高不明显(P=0.944,P=0.73s)。存活组14例,未存活组9例。急性期、恢复期或病情恶化时的三种细胞因子均显著高于正常对照(P<0.05)。存活组恢复期的TGF-α显著高于急性期(P=0.042),TNF-α、IL-1β比急性期升高,但差异不显著(P=0.948,P=0.992)。未存活组病情恶化时的TGF-α、IL-1β也明显高于急性期(P=0.050,P=0.062),TNF-α略升高(P=0.567)。两种炎症细胞因子在重型肝炎的发生、发展中起重要作用。TGF-α的血清浓度似乎影响病情转归。     

神经生长因子、白血病抑制因子调控支气管哮喘大鼠神经源性炎症机制的研究

目的研究神经生长因子(NGF)、白血病抑制因子(LIF)调控支气管哮喘(简称哮喘)大鼠气道神经源性炎症的机制,寻求治疗哮喘的新靶点。方法成年清洁级雄性SD大鼠36只,按随机数字表法分为对照组、哮喘组和抗NGF组,每组12只。采用免疫组织化学和原位杂交技术观察哮喘大鼠肺组织、C7～T5背根神经节内NGF、LIF、P物质(SP)的表达状态及抗NGF干预对其表达的影响。结果(1)哮喘组大鼠肺组织NGF、LIF蛋白及其mRNA的平均灰度值分别为157±7、138±8、156±6、141±10,对照组分别为183±7、190±7、187±7、181±8,抗NGF干预组分别为177±6、169±9、178±7、172±9,三组比较差异有统计学意义(t分别=19.40、15.80、0.38、14.79,P均<0.01);(2)哮喘组大鼠C7～T5背根神经节NGF、LIF、SP蛋白及SPmRNA的灰度值分别为136±8、148±6、140±8、128±8,对照组分别为185±7、187±8、174±7、180±8,抗NGF干预组分别为164±6、170±8、163±9、157±7,三组比较差异有统计学意义(t分别=29.50、22.65、23.12、28.71,P均<0.01)。结论促进背根神经节细胞合成和释放SP可能是NGF、LIF参与哮喘气道神经源性炎症形成的机制之一,抗NGF干预能够有效地将其抑制。