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.     

Cardiovascular reflexes and low long-term exposure to mercury vapour

Summary Subjective symptoms related to autonomic dysfunction and quantitative non invasive tests measuring both sympathetic and parasympathetic functions of the autonomic nervous system were studied among a group of 41 chlorine-alkali workers with low long-term exposure to mercury (Hg') vapour and their matched referents. The test battery included measurements of pulse rate variation in normal and deep breathing, in the Valsalva manoeuvre and in vertical tilt as well as blood pressure responses during standing and isometric work. The exposure time had been 16 years on average, and the mean exposure to Hg vapour was estimated to have been about 30 g/m³ of air. Only a tendency for a subtle reduction of cardiovascular reflex responses and a slight increase of subjective symptoms were seen in the exposed group, but no significant autonomic dysfunction was associated with the low level of exposure.     

Infrared spectroscopy: A new diagnostic tool in Alzheimer disease

Biological markers play an evolving role in the diagnosis of Alzheimer disease (AD). We compare conventional measurements of cerebrospinal fluid (CSF) tau and β-amyloid_1–42 proteins to a novel approach – Fourier transformed infrared (FT-IR) spectroscopy – a simple technique derived from chemical and physical sciences that characterizes intramolecular bonds. For automatic diagnostic analysis, we developed an artificial neural network (ANN). We examined 71 patients with a clinical diagnosis of AD and 66 controls. β-Amyloid_1–42 was decreased (sensitivity 80% and specificity 78%); tau was elevated (sensitivity 76% and specificity 88%) in CSF of AD patients. The combined tau/β-amyloid_1–42 quotient was able to distinguish healthy from diseased subjects with 99% sensitivity and 86% specificity. The ANN could separate FT-IR spectroscopy data with 88.5% sensitivity and 80% specificity. FT-IR spectroscopy proved to be cost-effective and simple to perform. Diagnostic sensitivity and specificity is in the range of CSF tau and β-amyloid_1–42 protein analysis. Larger sample numbers for ANN training and validation could increase diagnostic accuracy and thus prove to be a useful screening tool.     

消化还原一体化冷原子吸收法测定发中汞

目的：防止生物样品中的汞在消化过程中的逸失及在测量过程中由于汞的吸附造成器皿的污染。方法：采用消化还原一体化,在恒温水浴锅与自制恒温消化器消化样品,冷原子吸收法测定发中汞。结果：标准偏差小于０．０１３μｇ／ｇ;变异小于１０．２％;样品加标回收率介于８９％￣１０６％。结论：本方法有效地防止了汞的逸失及对器皿的污染,精密度与准确度均符合微量分析的要求。     

Degradation of methyl and ethyl mercury into inorganic mercury by oxygen free radical-producing systems: Involvement of hydroxyl radical

Degradation of methyl mercury (MeHg) and ethyl Hg (EtHg) with oxygen free radicals was studied in vitro by using three well-known hydroxyl radical (OH)-producing systems, namely Cu²⁺-ascorbate, xanthine oxidase (XOD)-hypoxanthine (HPX)-Fe(III)EDTA and hydrogen peroxide (H₂O₂)-ultraviolet light B. For this purpose, the direct determination method for inorganic Hg was employed. MeHg and EtHg were readily degraded by these three systems, though the amounts of inorganic Hg generated from MeHg were one half to one third those from EtHg. Degradation activity of XOD-HPX-Fe(III)EDTA system was inhibited by Superoxide dismutase, catalase and the OH scavengers and stimulated by H₂O₂. Deletion of the OH formation promoter Fe(III)EDTA from XOD-HPX-Fe(III)EDTA system resulted in the decreased degradation of MeHg and EtHg, which was enhanced by further addition of the iron chelator diethylenetriamine pentaacetic acid. In all these cases, a good correlation was observed between alkyl Hg degradation and deoxyribose oxidation determining OH. By contrast, their degradation appeared to be unrelated to either Superoxide anion production or H₂O₂ production alone. We further confirmed that H₂O₂ (below 2 mM) itself did not cause significant degradation of MeHg and EtHg. These results suggested that OH, but not and H₂O₂, might be the oxygen free radical mainly responsible for the degradation of MeHg and EtHg.     

Comparison of renal function and psychomotor performance in workers exposed to elemental mercury

Summary Renal function and psychomotor performance (eye-hand coordination, arm-hand steadiness) of a group of 43 workers exposed to mercury vapor were examined. Their mean age and average duration of exposure to mercury were 38 and 5 years, respectively. The results were compared with those obtained in a matched group of 47 control workers. Increased proteinuria and albuminuria were found slightly more prevalent in the Hg-exposed group than in the control workers. These results are in agreement with those found during a previous study carried out in another group of workers also exposed to elemental mercury (Bucket et al. 1980). The scores of the psychomotor tests were less satisfactory in the Hg workers than in the control workers, the arm-hand steadiness test being more discriminative than the eye-hand coordination test. Preclinical changes in psychomotor function can be detected independently of the presence of signs of renal dysfunction. No clear-cut relationships were found between the prevalence of abnormal psychomotor scores and the level of mercury in blood (HgB) or in urine (HgU). Increased prevalences of abnormal psychomotor scores seem however to occur for HgB between 1 and 2 g/100 ml and for HgU between 50 and 100 g/g creatinine. Therefore, a biologic threshold limit value of 50 g/g creatinine is proposed for urinary mercury to prevent the development of preclinical effects on the central nervous system. A similar critical HgU level based on renal dysfunction prevalences has been suggested in a previous study.This study was supported by a grant from the Commission of the European Communities     

Mercury-induced necrosis of murine renal cell carcinoma

Administration of the nephrotoxic agent, bichloride of mercury (HgCl₂), to BALB/c mice bearing subcapsular renal tumor transplants induced early preferential necrosis of the tumor cells compared with mercury-treated normal kidney tubular cells and untreated control tumors. The principle is established that a selective proximal tubular poison is also toxic for a tumor of the same cellular origin.     

Study of preclinical changes in workers exposed to inorganic mercury in chloralkali plants

Summary The aim of the present work was to clarify the question of preclinical changes of Hg intoxication (micromercurialism) in man. The study to detect these disorders was performed on 39 chloralkali plant workers who had been exposed to mercury for more than 7 years. The ambient air, urine and blood values of the last few years were determined in extensive measurements by various methods and related to one another. The average ambient air concentrations were clearly below the currently applicable threshold limit value (German MAK) of 0.1 mg/m³. For the purpose of clarifying the mentioned question of preclinical changes of intoxication, the exposed persons were subjected to psychomotor-function examinations and compared with a group of nonexposed persons. The blood pressure and pulse frequency values of both groups were also determined and compared with one another. No significant differences between the two groups of persons examined were detectable.Presented at the 18th Congress of the Deutsche Gesellschaft für Arbeitsmedizin in Frankfurt, 24th May 1978     

Effects of thimerosal on NGF signal transduction and cell death in neuroblastoma cells.

Signaling through neurotrophic receptors is necessary for differentiation and survival of the developing nervous system. The present study examined the effects of the organic mercury compound thimerosal on nerve growth factor signal transduction and cell death in a human neuroblastoma cell line (SH-SY5Y cells). Following exposure to 100 ng/ml NGF and increasing concentrations of thimerosal (1 nM-10 microM), we measured the activation of TrkA, MAPK, and PKC-delta. In controls, the activation of TrkA MAPK and PKC-delta peaked after 5 min of exposure to NGF and then decreased but was still detectable at 60 min. Concurrent exposure to increasing concentrations of thimerosal and NGF for 5 min resulted in a concentration-dependent decrease in TrkA and MAPK phosphorylation, which was evident at 50 nM for TrkA and 100 nM for MAPK. Cell viability was assessed by the LDH assay. Following 24-h exposure to increasing concentrations of thimerosal, the EC50 for cell death in the presence or absence of NGF was 596 nM and 38.7 nM, respectively. Following 48-h exposure to increasing concentrations of thimerosal, the EC50 for cell death in the presence and absence of NGF was 105 nM and 4.35 nM, respectively. This suggests that NGF provides protection against thimerosal cytotoxicity. To determine if apoptotic versus necrotic cell death was occurring, oligonucleosomal fragmented DNA was quantified by ELISA. Control levels of fragmented DNA were similar in both the presence and absence of NGF. With and without NGF, thimerosal caused elevated levels of fragmented DNA appearing at 0.01 microM (apoptosis) to decrease at concentrations >1 microM (necrosis). These data demonstrate that thimerosal could alter NGF-induced signaling in neurotrophin-treated cells at concentrations lower than those responsible for cell death.