小鼠经口投镉的慢性毒性研究——病理形态学改变的探讨

选用昆明种小鼠60只,体重18～24克,随机分成三组,每组20只,雌雄各半。通过饮水染毒。一组正常对照,饮自来水,二组饮30ppm含镉水,三组饮300ppm含镉水,染毒时间三个半月。观察指标:体重增长速度、脏器系数、肝肾中镉含量、重点病理形态学改变(光镜和电镜)。结果,30ppm组小鼠肝肾组织有一定病变,300ppm组小鼠的光镜和电镜的病理形态学改变更为明显。提示,小鼠长期摄入镉可引起一定的损害。     

Lack of biliary excretion of Cd linked to an inherent defect of the canalicular isoform of multidrug resistance protein (cMrp) does not abnormally stimulate accumulation of Cd in the Eisai hyperbilirubinemic (EHB) rat liver

A new mutant, the Eisai hyperbilirubinemic (EHB) rat, shows no inherent expression of the canalicular isoform of the multidrug resistance protein (cMrp) in the liver. It has defective biliary secretion of organic anions such as bilirubin glucuronides, bromosulfophthalein (BSP), cysteinyl leukotrienes, glutathione (GSH) and bile acid sulfate and glucuronides. When rats were injected intravenously with CdCl₂, biliary excretion of Cd over 30 min was 0.28% and 0.004% of the total dose in Sprague-Dawley (SD) and EHB rats, respectively. Six SD rats and five EHB rats were fed a diet containing Cd. Bile Cd was detected at the level of 2 ng/20 min in SD rats, but not in EHB rats. There was no significant difference of hepatic Cd concentration between SD and EHB rats. Furthermore, there were no significant differences of renal and intestinal Cd, and hepatic and renal metallothionein (MT) concentrations between the SD and EHB groups. Biliary excretion of reduced-GSH for 20 min was 1.3 ± 0.3 mg and 3.6 ± 0.9 μg in SD and EHB rats, respectively. Our results suggest that hepatobiliary excretion of exogenous Cd is mediated mainly via carrier transport, including a cMrp or GSH carrier, but that the lack of the transport pathway does not contribute to abnormal accumulation of Cd in the liver. Received: 12 August 1996 / Accepted 7 November 1996     

镉对家兔离体胃平滑肌收缩活动的影响

目的 :探讨镉对离体胃平滑肌收缩活动的影响。方法 :本实验用不同剂量氯化镉溶液对离体胃肌条循环灌流 ,用张力换能器测定 ,二道生理记录仪描记肌条收缩活动指标。结果 :镉离子对肌条的主动张力 (PT)、基础张力 (RT)、主动张力最大收缩速率 (dT/dtmax)和主动张力最大舒张速率 ( -dT/dtmax)均有明显抑制作用 ,而且呈剂量效应关系。这些作用可被乙酰胆碱对抗。结论 :镉离子可直接引起胃平滑肌收缩力降低。     

True histiocytic lymphoma of the esophagus in an HIV-positive patient: an ultrastructural study

A 56-year-old white woman, seropositive for human immunodeficiency virus for 18 months without signs of acquired immunodeficiency syndrome, presented with retrosternal pain and progressive dysphagia secondary to an exophytic esophageal mass. Biopsies of the tumor showed a malignant neoplasm composed of pleomorphic, noncohesive cells growing in a diffuse, sheet-like fashion. Immunohistochemically, tumor cells were nonreactive with epithelial, lymphoid, neural, and monocyte/macrophage markers. Despite the noncontributory immunohistochemical findings, ultrastructural study of the tumor cells revealed convincing histiocytic features. Individual cells possessed long, slender filopodial projections, prominent Golgi apparatus, residual bodies, rare lysosomes, and prelysosomes. Immunoglobulin heavy chain and T-cell receptor gamma gene rearrangement studies detected no evidence of a clonal gene rearrangement. The patient responded poorly to chemotherapy and died 5 months after her initial symptom of dysphagia.     

CD45 Isoform Expression in Autoimmune Myasthenia Gravis

In myasthenia gravis (MG), humoral and cellular immune mechanisms are involved in the autoimmune pathogenesis. In this study, we investigated the role of the CD45 molecule in MG, having recently reported an association in multiple sclerosis. CD45, a protein-tyrosine phophatase receptor type C (PTPRC), is essential for both thymic selection and peripheral activation of T and B cells. Our aims were to determine (a) the prevalence of a functional mutation in the CD45 gene (exon 4 77C &#77 G; prevalence analysis), and (b) the distribution of memory (CD45RO+) and naïve (CD45RA+) T cells in the peripheral blood (subset analysis). T cells from 78 patients with generalised MG were stained with monoclonal antibodies against CD45RO, CD45RA, CD4 and CD8 and quantified by four-colour flow cytometry. The control panel for the prevalence analysis (a) consisted of 303 healthy individuals. (b) From those, 67 age- and sex-matched probands were randomly selected as controls for the subset analysis. Patients were stratified according to their MG onset age, thymic pathology and immunosuppressive treatment. Statistical analysis was performed by Fisher's exact test, asymptotic &#104 2 test, the two-sided Mann-Whitney test and Spearman's correlation coefficient. As a result, the 77C &#77 G mutation in exon 4 of the CD45 gene was found in 1 of 78 patients versus none of the 303 controls. Thus, no association was detected with this single nucleotide polymorphism in MG patients overall. Surprisingly, however, ratios of CD45RO+ to CD45RA+ T cells were lower among CD8+ T cells from patients with late-onset MG ( P =0.023). Thymoma patients also showed a similar trend among CD4+ and CD8+ T-cells, as expected. These differences were not related to immunosuppressive drug treatment or thymectomy (in the 67 informative patients). Since there is no other evidence for increased thymopoiesis in late-onset MG, we propose an altered subset balance in the circulation.     

In vitro immunotoxicology of quantum dots and comparison with dissolved cadmium and tellurium

The increasing use of products derived from nanotechnology has raised concerns about their potential toxicity, especially at the immunocompetence level in organisms. This study compared the immunotoxicity of cadmium sulfate/cadmium telluride (CdS/Cd‐Te) mixture quantum dots (QDs) and their dissolved components, cadmium chloride (CdCl₂)/sodium telluride (NaTeO₃) salts, and a CdCl₂/NaTeO₃ mixture on four animal models commonly used in risk assessment studies: one bivalve (Mytilus edulis), one fish (Oncorhynchus mykiss), and two mammals (mice and humans). Our results of viability and phagocytosis biomarkers revealed that QDs were more toxic than dissolved metals for blue mussels. For other species, dissolved metals (Cd, Te, and Cd‐Te mixture) were more toxic than the nanoparticles (NPs). The most sensitive species toward QDs, according to innate immune cells, was humans (inhibitory concentration [IC₅₀] = 217 μg/mL). However, for adaptative immunity, lymphoblastic transformation in mice was decreased for small QD concentrations (EC₅₀ = 4 μg/mL), and was more sensitive than other model species tested. Discriminant function analysis revealed that blue mussel hemocytes were able to discriminate the toxicity of QDs, Cd, Te, and Cd‐Te mixture (Partial Wilk's λ = 0.021 and p < 0.0001). For rainbow trout and human cells, the immunotoxic effects of QDs were similar to those obtained with the dissolved fraction of Cd and Te mixture. For mice, the toxicity of QDs markedly differed from those observed with Cd, Te, and dissolved Cd‐Te mixture. The results also suggest that aquatic species responded more differently than vertebrates to these compounds. The results lead to the recommendation that mussels and mice were most able to discriminate the effects of Cd‐based NPs from the effects of dissolved Cd and Te at the immunocompetence level. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 9–25, 2015.     

A silver enhanced and sensitive strip sensor for Cadmium detection

In this study, an enhanced test strip, based on a monoclonal antibody for the cadmium-ethylenediaminetetraacetic acid (EDTA) complex, but not metal-free EDTA, has been developed. This colorimetric sensor was sensitive and specific for the detection of cadmium in aqueous samples containing excess EDTA. Through a process of silver enhancement, the visual detection limit for Cd(II) was 5 µg/L under optimised conditions and the limit of detection for semi-quantitative detection could be as low as 0.35 µg/L by using a scanning reader. The calibration curve showed that the colour intensity decreased as the Cd(II) concentration increased in the range of 0.5–5 µg/L. The other metal ions did not interfere with the determination of Cd(II). The recoveries of drinking water samples were from 98 to 108%. Consequently, the assay could be employed as a potential on-site screening tool for the detection of Cd(II) in water samples.     

NTPDase and 5′-nucleotidase activities from synaptosomes and platelets of rats exposed to cadmium and treated with N-acetylcysteine

The purpose of the present investigation was to evaluate the hydrolysis of adenine nucleotides on synaptosomes and platelets obtained from rats exposed to cadmium (Cd) and treated with N-acetylcysteine (NAC). Rats received Cd (2 mg/kg) and NAC (150 mg/kg) by gavage every other day for 30 days. Animals were divided into four groups (n = 4–6): control/saline, NAC, Cd, and Cd/NAC. The results of this study demonstrated that NTPDase and 5′-nucleotidase activities were increased in the cerebral cortex synaptosomes of Cd-poisoned rats, and NAC co-treatment reversed these activities to the control levels. In relation to hippocampus synaptosomes, no differences on the NTPDase and 5′-nucleotidase activities of Cd-poisoned rats were observed and only the 5′-nucleotidase activity was increased by the administration of NAC per se. In platelets, Cd-intoxicated rats showed a decreased NTPDase activity and no difference in the 5′-nucleotidase activity; NAC co-treatment was inefficient in counteracting this undesirable effect. Our findings reveal that adenine nucleotide hydrolysis in synaptosomes and platelets of rats were altered after Cd exposure leading to a compensatory response in the central nervous system and acting as a modulator of the platelet activity. NAC was able to modulate the purinergic system which is interesting since the regulation of these enzymes could have potential therapeutic importance. Thus, our results reinforce the importance of the study of the ecto-nucleotidases pathway in poisoning conditions and highlight the possibility of using antioxidants such as NAC as adjuvant against toxicological conditions.     

ICP-MS法测定喜炎平注射液中重金属及有害元素

目的 建立喜炎平注射液中17种重金属及有害元素的含量测定方法。方法 样品经消解后采用电感耦合等离子体质谱（ICP-MS）法测定,射频功率1 550 W;蠕动泵转速0.3 r/s;等离子气体积流量15 L/min;辅助气体积流量0.2 L/min;载气体积流量1 L/min;采样深度10 mm,重复次数为3次。结果 该方法下Li、Al、V、Cr、Fe、Co、Ni、Cu、As、Ag、Cd、Sn、Sb、Ba、Hg、Pb、Bi的检测限分别为9.584、49.858、0.504、3.016、51.209、0.142、1.116、0.675、0.924、1.421、0.403、2.770、0.711、3.584、0.590、0.411、0.169 ng/mL,定量限分别为28.933、151.085、1.528、9.139、155.179、0.429、3.381、2.046、2.799、4.312、1.220、8.394、2.155、10.861、1.965、1.244、0.513 ng/mL,各元素在一定质量浓度范围内,响应值与质量浓度的线性关系良好（r>0.999 1）,进样精密度RSD在0.8%~3.8%（n=12）,重复性RSD在0.7%~2.0%（n=6）,17种元素的加样回收率在95.7%~104.8%。20批大生产样品检测结果：Ag为未检出,Li和V为检出但低于定量限,Al、Ni、Cu、As、Ba、Hg、Pb最大质量浓度分别为0.685、0.013、0.007、0.006、0.208、0.070、0.027 μg/mL,Cr、Fe、Co、Cd、Sn、Sb、Bi为未检出或检出但低于定量限。结论 方法的专属性、线性、灵敏度、精密度、准确度、耐用性等均良好,可用于喜炎平注射液中Li、Al、V、Cr、Fe、Co、Ni、Cu、As、Ag、Cd、Sn、Sb、Ba、Hg、Pb、Bi 17种元素的含量测定,20批大生产样品中17种元素检测结果均小于限度要求,符合规定。