Gold complex research in medical science. Difficulties with experimental design

Despite the use of gold complexes in modern medicine for over 100 years and the use of gold complexes in the management of rheumatoid disease for more than 60 years, the definitive mechanisms of action for efficacy and for toxicity have not been established. Gold is a group 1b metal in the periodic table with several oxidation states but it is only Au(I) which is active in the biological milieu. Gold sodium thiomalate is not only a polymeric structure, but also has the chiral ligand, thiomalic acid. Gold sodium thiomalate thus can exist in several different physical states which may have different biological activity. In addition the pharmacokinetic profile of gold complexes has been of little value in the understanding of either the mechanism of action, efficacy or toxicity for both the injectable and the oral gold complexes. Many authors have misinterpreted research data on the activities of gold complexes because they compared gold complexes of different structures, and gold complexes which exist at different pH. Experimental work in our laboratory has identified that gold sodium thiomalate is a mixture and can exist as either a yellow or a colourless solution. These have some similar but several different biological activities. Many factors contribute to the lack of understanding of the action of gold complexes. Some of these factors are related to the wide variation in physical structure and biological activities exhibited by these compounds.     

Some investigations into the nature and cause of massive fibrosis (MF) in the lungs of South African gold, coal, and asbestos mine workers

Samples from fibrotic lung lesions greater than 1 cm in diameter macroscopically (by definition, massive fibrosis; MF) were taken from the lungs of 9 randomly selected post-mortem cases of mine workers all showing a background of a pneumoconiosis. These samples were studied histologically, biochemically, and by X-ray diffraction and electron microscopy. As controls for the biochemical and X-ray diffraction investigations, nonfibrosed lung tissue was taken from the same specimens. The findings suggest that the higher quartz content may be the primary cause responsible for the MF formation in this series of cases, while other factors such as tuberculosis may play a part according to some relevant literature on MF. Although an area of MF appears macroscopically to be a solid lesion, on microscopy this is not the case and the lesion is composed of dense and sparse collagen bundles and cellular elements.     

用金标法快速测定血清中cTn-Ⅰ在急性心肌梗死诊断上的应用

为探讨急性心肌梗死和疑为心梗病人血中 c Tn I的敏感性和特异性 ,采用金标法对 5 2例就诊病人测定其血中 c Tn- 和酶学法测定 CK- MB两个指标 ,结果发现急性心肌梗死组病人血中的 c Tn- 敏感度高于 CK- MB,但二者无显著性差异 ;而疑为心梗病人血中的 c Tn- 敏感度高于 CK- MB且具有显著的特异性。c Tn- 的测定对急性心肌梗死病人的诊断和治疗具有特别重要的意义     

Gold: an old drug still working in refractory pemphigus

BACKGROUND: The mainstay of treatment for pemphigus is systemic corticosteroids. Different adjuvants have been used to reduce side-effects of long-term corticotherapy. Gold is an anti-inflammatory drug used in autoimmune diseases, whose use has waned with the advent of new immunosuppressive agents. OBJECTIVE: To study the outcome of the use of intramuscular gold treatment of pemphigus vulgaris refractory to previous therapies. METHODS: Thirteen patients with pemphigus vulgaris who had failed to respond to several prior therapies were treated with aurothiomalate, as a steroid-sparing agent. Patients were monitored to assess disease activity and gold toxicity. RESULTS: Seven patients achieved complete remission. Four patients were able to taper prednisone doses, although pemphigus flared when prednisone was discontinued or reduced. Toxicity was observed in the other two patients. CONCLUSIONS: In 53.4% of the patients, the use of chrysotherapy resulted in the complete clearing of the disease, discontinuation of all systemic therapies and induced a long-term clinical remission. Prednisone doses were able to be reduced in the remaining 46.6%. Any side-effects were reversible with drug discontinuation. Gold therapy showed efficacy as a secondary line treatment in refractory pemphigus vulgaris.     

A retrospective mortality study of workers exposed to arsenic in a gold mine and refinery in France

A historical mortality study of a cohort of employees of a gold mining and refining company was carried out in Salsigne, France. A major goal of the study was to investigate the relationship between lung cancer mortality and exposure to arsenic, radon, silica, and other contaminants of the working environment. A twofold excess of lung cancer was found both among miners and smelters, mainly concentrated among workers who had experienced exposure to past levels of arsenic, radon, and silica. The consistency of the results in the mine and the refinery are suggestive of a carcinogenic risk from both soluble and insoluble arsenic, although the potential role of other factors cannot be dismissed. © 1994 Wiley-Liss, Inc.     

Oral lichenoid lesions, mercury hypersensitivity and combined hypersensitivity to mercury and other metals: histologically-proven reproduction of the reaction by patch testing with metal salts

We report 11 patients seen between 1991 and 1994 with oral lichenoid lesion(OLL). In 10 cases, there was contact with dental amalgam fillings, and in patient no. 10 with both amalgam restorations and a gold crown. The last patient had, in addition to her OLL, lichen planus of the skin and genital mucosa. In 5 cases, combined sensitization to mercury and other metal salts, particularly gold sodium thiosulfate (GST) and palladium chloride (PDC), was observed. In 10 patients, the lesions considerably improved or totally cleared within 1 to 9 months of replacement of restoration materials. Histological examination of biopsies from the test sites of amalgam, mercuric chloride, GST and PDC, taken 10 or 17 days, after application of patch tests, showed lichenoid changes in 7 patients with at least 1 of the allergens. At least 2 patients had inflammatory lesions of the oral mucosa related to both amalgam and gold restorations, combined sensitization to inorganic and organic mercury derivatives. GST and, in 1 case, PDC, a "dental restoration metal intolerance syndrome" is proposed.     

免疫层析法用于HCG快速检测的研究

目的：研制用于尿液HCG快速检验试纸条。方法：采用胶体金免疫层析分析方法。结果：检测灵敏度可达50IU／L，与高含量的LH、FSH、TSH均无交叉反应，检测214例临床样品，准确率为100％。结论：该方法简单、快速、特异性强，是检测尿液HCG较好的免疫学方法。     

Relationship of actin filament assembly to clearance of fibrinogen gold, GPIIb-IIIa complexes on spread platelets

Abstract. The present study has evaluated the influence of high concentrations of cytochalasins B and E on the detergent-resistant actin levels in fully spread platelets by PAGE gel electrophoresis, and the effects of the two inhibitors of new actin filament assembly on translocation of fibrinogen gold (Fgn/Au) labelled GPIIb-IIIa receptors on the surface-activated cells. Concentrations of 10^{- 4}m and 10^-5 m cytochalasin B and E reduced detergent-resistant actin in fully spread platelets to levels present in resting discoid platelets in suspension. Despite reduction of actin filaments to levels in resting cells, cytochalasin B did not prevent translocation of Fgn/Au from platelet margins into channels of the open canalicular system (OCS). Similar concentrations of cytochalasin E completely blocked translocation of receptor-ligand complexes and produced a patching phenomenon not observed in previous studies. Rinsing of the spread cells to remove cytochalasin, followed by incubation of the treated platelets in Hank's buffered salt solution (HBSS) restored levels of detergent-resistant actin to those found in untreated, spread platelets. Resting grids of 10 ⁵ m cytochalasin E-treated platelets on drops of HBSS for 15min restored their ability to clear FGN/Au linked to GPIIb-IIIa from exposed surfaces to the OCS, but 10^-4 m cytochalasin E-treated cells remained anergic after incubation on drops of HBSS. Thus a fully assembled cytoplasmic actin filament cytoskeleton does not appear to be essential for translocating receptor-ligand complexes on the platelet surface to the OCS, nor does its presence guarantee that the ability to clear GPIIb-IIIa receptors will be restored.     

呼吸道真菌感染核酸胶体金试纸条快速检测方法的建立和评价

目的 采用聚合酶链式反应（PCR）技术和胶体金技术建立一种呼吸道真菌感染核酸胶体金试纸条检测方法,并对其检测效果进行评价。 方法 根据GenBank数据库选择真菌内转录间隔区（ITS）基因片段作为靶基因,应用DNAMAN软件对真菌ITS基因片段进行分析,并分别在真菌通用引物5'端用生物素（Biotin）和异硫氰酸荧光素（FITC）进行修饰标记;建立PCR体系,进行体系的最佳条件优化;确定胶体金免疫层析试纸条标记链霉亲和素的最佳标记量和质控线及检测线最佳包被物浓度,组装核酸胶体金试纸条,对试纸条的特异度、灵敏度、重复性和稳定性进行验证。 结果 水煮法提取白假丝酵母菌、新生隐球菌和毛霉菌DNA,浓度为180 μg·L^－1以上,纯度为1.60~2.10;在pH 7.0条件下,每100 μL胶体金溶液中制备胶体金标记链霉亲和素最佳标记量为 3.3 μg,质控线包被Biotin化牛血清白蛋白（BSA-Biotin）浓度为2.00 g·L^－1,检测线包被抗FITC抗体浓度为1.00 g·L^－1。核酸试纸条的特异度与电泳结果一致,仅白假丝酵母菌、新生隐球菌和毛霉菌出现阳性结果,与金黄色葡萄球菌、肺炎链球菌、乙型溶血性链球菌、铜绿假单胞菌、肺炎克雷伯菌、鲍曼不动杆菌和大肠埃希菌等常见呼吸道感染细菌无交叉反应。灵敏度检测,白假丝酵母菌、新生隐球菌和毛霉菌的DNA浓度分别为10^－4、10^－2和10^－3 mg·L^－1时核酸试纸条仍可准确检出,而普通PCR电泳结果显示白假丝酵母菌、新生隐球菌和毛霉菌最低检测浓度分别为0.01、1.00和0.10 mg·L^－1;重复性检测,在不同实验室不同操作人员对核酸试纸条进行验证,结果一致,重复性良好;稳定性检测,核酸试纸条在第6、9和12个月进行检测,结果符合预期,稳定性良好。 结论 本研究建立的呼吸道真菌感染核酸胶体金试纸条可以检测白假丝酵母菌、新生隐球菌和毛霉菌等真菌,特异度和灵敏度均较高,操作简便且快速。