Digital Thermal Necrosis Resulting in Amputation After Removing a Tungsten Carbide Ring With a High-Speed Metal Burr: A Case Report.

CASE: A 41-year-old man removed a tungsten carbide ring from his left index finger by cutting it off with a high-speed metal burr. The patient presented two days later with a pink and perfused left index finger with circumferential dry gangrene along the area of the ring, active flexor and extensor tendon excursion, and decreased sensation distally. Within 24 hours, the wound developed into wet gangrene and diffuse cyanosis requiring amputation. CONCLUSION: After reviewing previously documented methods to remove tungsten carbide rings, the authors conclude clinicians should be cognizant of the potential complications associated with the use of a high-speed metal burr.

Thyroid Stem Cells But Not Differentiated Thyrocytes Are Sensitive to Slightly Increased Concentrations of Heavy Metals.

Thyroid cancer incidence is markedly increased in volcanic areas where residents are biocontaminated by chronic lifelong exposure to slightly increased metals in the environment. Metals can influence the biology of living cells by a variety of mechanisms, depending not only on the dose and length of exposure but also on the type and stage of differentiation of target cells. We explored the effect of five heavy metals (Cu, Hg, Pd, W and Zn) at nanomolar concentrations (the biocontamination level in residents of the volcanic area in Sicily where thyroid cancer is increased) on stimulating the proliferation of undifferentiated (thyrospheres) and differentiated human thyroid cells. Thyrosphere proliferation was significantly increased after exposure to each individual metal and a greater stimulating effect was observed when a mixture of the examined metals was used. No effect was seen in differentiated thyrocytes. For all metals, the dose-response curve followed a biphasic pattern that is typical of hormesis. Thyrosphere growth concerned the size rather than number, except with the metal mixture. An altered morphology was also observed in metal-treated thyrospheres. Metal-induced proliferation was due to activation of the ERK1/2 pathway, as confirmed by growth inhibition when ERK1/2 signaling was blocked. These studies show that stem/precursor thyroid cells are sensitive to small increases in environmental metal concentrations that are harmless for differentiated thyrocytes.

Long-term effects of tungsten carbide (WC) nanoparticles in pelagic and benthic aquatic ecosystems.

As the production and usage of nanomaterials are increasing so are the concerns related to the release of the material into nature. Tungsten carbide (WC) is widely used for its hard metal properties, although its use, in for instance tyre studs, may result in nano-sized particles ending up in nature. Here, we evaluate the potential long-term exposure effects of WC nanoparticles on a pelagic (Daphnia magna) and a benthic (Asellus aquaticus) organism. No long-term effects were observed in the benthic system with respect to population dynamics or ecosystem services. However, long-term exposure of D. magna resulted in increased time to first reproduction and, if the particles were resuspended, strong effects on survival and reproductive output. Hence, the considerable differences in acute vs. long-term exposure studies revealed here emphasize the need for more long-term studies if we are to understand the effects of nanoparticles in natural systems.

Nanotoxicity: emerging concerns regarding nanomaterial safety and occupational hard metal (WC-Co) nanoparticle exposure.

As the number of commercial and consumer products containing engineered nanomaterials (ENMs) continually rises, the increased use and production of these ENMs presents an important toxicological concern. Although ENMs offer a number of advantages over traditional materials, their extremely small size and associated characteristics may also greatly enhance their toxic potentials. ENM exposure can occur in various consumer and industrial settings through inhalation, ingestion, or dermal routes. Although the importance of accurate ENM characterization, effective dosage metrics, and selection of appropriate cell or animal-based models are universally agreed upon as important factors in ENM research, at present, there is no "standardized" approach used to assess ENM toxicity in the research community. Of particular interest is occupational exposure to tungsten carbide cobalt (WC-Co) "dusts," composed of nano- and micro-sized particles, in hard metal manufacturing facilities and mining and drilling industries. Inhalation of WC-Co dust is known to cause "hard metal lung disease" and an increased risk of lung cancer; however, the mechanisms underlying WC-Co toxicity, the inflammatory disease state and progression to cancer are poorly understood. Herein, a discussion of ENM toxicity is followed by a review of the known literature regarding the effects of WC-Co particle exposure. The risk of WC-Co exposure in occupational settings and the updates of in vitro and in vivo studies of both micro- and nano-WC-Co particles are discussed.

Immunotoxic effects of sodium tungstate dihydrate on female B6C3F1/N mice when administered in drinking water.

Tungsten is a naturally occurring, high-tensile strength element that has been used in a number of consumer products. Tungsten has been detected in soil, waterways, groundwater, and human tissue and body fluids. Elevated levels of tungsten in urine were reported for populations exposed to tungstate in drinking water in areas where natural tungsten formations were prevalent. Published reports indicated that sodium tungstate may modulate hematopoiesis, immune cell populations, and immune responses in rodent models. The objective of this study was to assess potential immunotoxicity of sodium tungstate dihydrate (STD), a drinking water contaminant. Female B6C3F1/N mice received 0-2000 mg STD/L in their drinking water for 28 d, and were evaluated for effects on immune cell populations in spleen and bone marrow, and humoral-mediated, cell-mediated, and innate immunity. Three different parameters of cell-mediated immunity were similarly affected at 1000 mg STD/L. T-cell proliferative responses against allogeneic leukocytes and anti-CD3 were decreased 32%, and 21%, respectively. Cytotoxic T-lymphocyte activity was decreased at all effector:target cell ratios examined. At 2000 mg STD/L, the absolute numbers of CD3(+) T-cell progenitor cells in bone marrow were increased 86%, but the alterations in B-lymphocyte and other progenitor cells were not significant. There were no effects on bone marrow DNA synthesis or colony forming capabilities. STD-induced effects on humoral-mediated immunity, innate immunity, and splenocyte sub-populations were limited. Enhanced histopathology did not detect treatment-related lesions in any of the immune tissues. These data suggest exposure to STD in drinking water may adversely affect cell-mediated immunity.

A hard (metal) case: Value of analytical scanning electron microscopy.

Exposure to hard metal (tungsten carbide) dust is a rare cause of interstitial lung disease. Although most cases have a distinctive morphology known as giant cell interstitial pneumonitis, other patterns have been described as well. In such cases, the true nature of the interstitial process may be difficult to recognize. We present a case with unusual morphological features in which analytical scanning electron microscopy (SEM) was used to detect the presence of tungsten as well as other metallic particles. A combination of careful exposure history and examination by analytical SEM is useful for arriving at the correct diagnosis in such difficult cases.

Interactions of 1D- and 2D-layered inorganic nanoparticles with fibroblasts and human mesenchymal stem cells.

AIM: This study investigates the effects of tungsten disulfide nanotubes (WSNTs) and molybdenum disulfide nanoplatelets (MSNPs) on fibroblasts (NIH-3T3) and mesenchymal stem cells (MSCs) to determine safe dosages for potential biomedical applications. MATERIALS & METHODS: Cytotoxicity of MSNPs and WSNTs (5-300 µg/ml) on NIH-3T3 and MSCs was assessed at 6, 12 or 24 h. MSC differentiation to adipocytes and osteoblasts was assessed following treatment for 24 h. RESULTS: Only NIH-3T3 cells treated with MSNPs showed dose or time dependent increase in cytotoxicity. Differentiation markers of MSCs in treated groups were unaffected compared with untreated controls. CONCLUSION: MSNPs and WSNTs at concentrations less than 50 µg/ml are potentially safe for treatment of fibroblasts or MSCs for up to 24 h.

Elemental analysis of occupational and environmental lung diseases by electron probe microanalyzer with wavelength dispersive spectrometer.

Occupational and environmental lung diseases are a group of pulmonary disorders caused by inhalation of harmful particles, mists, vapors or gases. Mineralogical analysis is not generally required in the diagnosis of most cases of these diseases. Apart from minerals that are encountered rarely or only in specific occupations, small quantities of mineral dusts are present in the healthy lung. As such when mineralogical analysis is required, quantitative or semi-quantitative methods must be employed. An electron probe microanalyzer with wavelength dispersive spectrometer (EPMA-WDS) enables analysis of human lung tissue for deposits of elements by both qualitative and semi-quantitative methods. Since 1993, we have analyzed 162 cases of suspected occupational and environmental lung diseases using an EPMA-WDS. Our institute has been accepting online requests for elemental analysis of lung tissue samples by EPMA-WDS since January 2011. Hard metal lung disease is an occupational interstitial lung disease that primarily affects workers exposed to the dust of tungsten carbide. The characteristic pathological findings of the disease are giant cell interstitial pneumonia (GIP) with centrilobular fibrosis, surrounded by mild alveolitis with giant cells within the alveolar space. EPMA-WDS analysis of biopsied lung tissue from patients with GIP has demonstrated that tungsten and/or cobalt is distributed in the giant cells and centrilobular fibrosing lesion in GIP. Pneumoconiosis, caused by amorphous silica, and acute interstitial pneumonia, associated with the giant tsunami, were also elementally analyzed by EPMA-WDS. The results suggest that commonly found elements, such as silicon, aluminum, and iron, may cause occupational and environmental lung diseases.

PEGylated WS(2) nanosheets as a multifunctional theranostic agent for in vivo dual-modal CT/photoacoustic imaging guided photothermal therapy.

A new generation of photothermal theranostic agents is developed based on PEGylated WS2 nanosheets. Bimodal in vivo CT/photoacoustic imaging reveals strong tumor contrast after either intratumoral or intravenous injection of WS2 -PEG. In vivo photothermal treatment is then conducted in a mouse tumor model, achieving excellent therapeutic efficacy with complete ablation of tumors. This work promises further exploration of transition-metal dichalcogenides for biomedical applications, such as cancer imaging and therapy.

Induction of miR-21-PDCD4 signaling by tungsten carbide-cobalt nanoparticles in JB6 cells involves ROS-mediated MAPK pathways.

Tungsten carbide-cobalt (WC-Co) nanoparticle composites have wide applications because of their hardness and toughness. WC-Co was classified as "probably carcinogenic" to humans by the International Agency for Research on Cancer (IARC) in 2003. It is believed that the toxicity and carcinogenesis of WC-Co is associated with particle size. Recent studies demonstrated that the tumor suppressor gene programmed cell death 4 (PDCD4) and its upstream regulator miR-21 have been considered as oncogenes for novel cancer prevention or anticancer therapies. The present study examined the effects of WC-Co nanoparticles on miR-21-PDCD4 signaling in a mouse epidermal cell line (JB6 P+). The results showed that (i) exposure of JB6 cells to WC-Co stimulated a increase of miR-21 generation; (ii) WC-Co also caused inhibition of PDCD4, a tumor suppressor protein and downstream target of miR-21, expression in JB6 cells; (iii) inhibition of ERKs with ERK inhibitor U0126 significantly reversed WC-Cominus;induced PDCD4 inhibition, but inhibition of p38 with p38 inhibitor SB203580 did not; and (iv) ROS scavengers, N-acetyl-L-cysteine and catalase, blocked the inhibitory effect of WC-Co on PDCD4 expression, while superoxide dismutase promoted the inhibitory effect. These findings demonstrate that WC-Co nanoparticles induce miR-21 generation, but inhibit PDCD4 production, which may be mediated through ROS, especially endogenous H2O2, and ERK pathways. Unraveling the complex mechanisms associated with these events may provide insights into the initiation and progression of WC-Co-induced carcinogenesis.

Development of worker inhalation derived no effect levels for tungsten compounds.

Under the European Community (EC) Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), the risk to humans may be considered controlled if the estimated exposure levels to a substance do not exceed the appropriate derived no-effect level (DNEL). In order to address worker exposure, DNELs are derived for the worker population. The most significant route of exposure to workers to both soluble and sparingly soluble tungsten substances is through inhalation. In order to meet the REACH registration requirements, occupational long-term inhalation DNELs were developed according to the European Chemical Agency (ECHA) REACH guidance on characterization of dose-response for human health. The inhalation DNELlong-term for sodium tungstate, from which all other soluble tungsten substance DNELs were derived, is 3 mg sodium tungstate/m(3) (1.7 mg W/m(3)), and the inhalation DNELlong-term for tungsten blue oxide, from which all other sparingly soluble tungsten substance DNELs were derived, is 7.3 mg tungsten blue oxide/m(3) (5.8 mg tungsten/m(3)). Although derived using different methodologies and supported by different studies, the occupational inhalation DNELslong-term for soluble and sparingly soluble tungsten compounds are similar to the current National Institute for Occupational Safety and Health (NIOSH) recommended exposure level (REL) and the American Conference of Industrial Hygienists (ACGIH) threshold limit value (TLV) 8-h time weighted average (TWA) of 1 mg tungsten/m(3) for soluble tungsten compounds and 5 mg tungsten/m(3) as metal and insoluble tungsten compounds.

An in vitro investigation of the effectiveness of bioactive glass air-abrasion in the 'selective' removal of orthodontic resin adhesive.

The process of clinically debonding orthodontic brackets causes histomorphological damage to enamel that needs to be quantified and minimized. This study compared three methods for removing residual resin adhesive following bracket debonding. The surface finish following removal of residual adhesive using a slow-speed eight-bladed tungsten carbide bur (group 1), alumina air-abrasion (group 2), and bioactive-glass air-abrasion (group 3) and following polishing, was examined using scanning electron microscopy imaging of resin replicas. Contact profilometry was used to image surfaces before and after debonding for quantifiable volumetric analysis of enamel damage. Surface scarring was seen on scanning electron micrographs from group 1, a sharp pitted surface was identified in group 2, while group 3 exhibited similar, but subjectively smoother, pits. The surface finish following polishing was similar for groups 2 and 3 but did not completely remove the scarring evident from group 1. Quantifiable enamel lost was as follows: group 1, 0.285 mm(3); group 2, 0.386 mm(3); and group 3, 0.135 mm(3); statistical differences were observed between groups 2 and 3. From these results, bioactive-glass air-abrasion more consistently caused less physical damage to enamel and achieved a clinically smooth surface finish following polishing and is therefore to be recommended for clinical use.

Inferior alveolar nerve damage because of overextended endodontic material: a problem of sealer cement biocompatibility?

Damage to the inferior alveolar nerve is a relatively infrequent complication in dental practice. When root canal treatment of a lower molar or premolar surpasses and/or overextends beyond the apical foramen and invades the periapical zone, the foreign material introduced within such a sensitive anatomical space may mechanically or even chemically affect the inferior alveolar nerve. We describe a case of endodontic treatment of a permanent right lower first molar in which the sealer cement overextended in large amounts and damaged the right inferior alveolar nerve. The condition reverted a few months after the surgical removal of the material. Evaluation of the removed material, using powder x-ray diffraction and scanning electron microscopy with coupled dispersive energy spectroscopy, showed it to consist of calcium tungstate (scheelite [CaWO4]) and zirconium oxide (baddeleyite [ZrO2]), which were chemical components of the sealer cement.

[Analysis of morbidity in vicinity of a tungsten-molybdenum industrial complex].

Morbidity rates were analyzed in adults residing in vicinity of a tungsten-molybdenum industrial complex. The structure of morbidity was examined in relation to the physiological role of a number of heavy metals that are the priority contaminants in this area and with the habits of the residential population. The incidence of diseases of the musculoskeletal system, connective tissue, and respiratory organs was significantly higher in the area adjacent to the complex. In the mid-highlands, there are low incidence rates of circulatory, digestive, and urogenital diseases, and neoplasms as compared with the republican rates.

Two-dimensional analysis of elements and mononuclear cells in hard metal lung disease.

RATIONALE: Hard metal lung disease is caused by exposure to hard metal, a synthetic compound that combines tungsten carbide with cobalt as well as a number of other metals. Interstitial lung disease caused by hard metal is uniquely characterized by giant cell interstitial pneumonia. The pathogenesis of hard metal lung disease is unclear. OBJECTIVES: To elucidate the distribution of inhaled hard metal and reactive inflammatory cells in biopsy lung tissue from patients with hard metal lung disease. METHODS: Seventeen patients with interstitial lung disease in which tungsten was detected and five control subjects were studied. Detection and mapping of elements were performed with an electron probe microanalyzer equipped with a wavelength dispersive spectrometer. We immunohistochemically stained mononuclear cells, in tissue samples available from five patients, with anti-human CD4, CD8, CD20, CD68, and CD163 antibodies, and compared the distribution of positive cells with hard metal elements. MEASUREMENTS AND MAIN RESULTS: Thirteen of 17 patients were pathologically diagnosed as having giant cell interstitial pneumonia. Tungsten and cobalt were accumulated in the centrilobular fibrotic lesions, but were never found in the control lungs. CD8+ lymphocytes and CD163+ monocyte-macrophages were distributed predominantly in centrilobular fibrotic lesions around the hard metal elements. CD163+ colocalized with tungsten. Small numbers of CD8+ and CD163+ cells were also immunohistochemically shown in peribronchiolar areas and alveolar walls. CONCLUSIONS: Macrophages may phagocytose inhaled tungsten via CD163 and play an important role in forming the fibrotic lesion of hard metal lung disease with cytotoxic T lymphocytes.

[A case of bronchiolitis possibly associated with inhalation of hard metal].

A 36-year-old man, a worker exposed to tungsten and cobalt compounds, was admitted because of chest bilateral micronodular shadow with chronic cough and sputum. Chronic sinusitis, mild hypoxemia, obstructive respiratory impairment and chest radiological findings fulfilled the Japanese diagnostic criteria for diffuse panbronchiolitis, while atypical bronchoalveolar lavage fluid and pathological findings were seen. The surgical lung biopsy specimens showed patchy centrilobular inflammatory change with monocytic infiltrations and particulate deposition inside the area of bronchiolitis, but neither tungsten nor cobalt was found. Treatment with a macrolide antibiotic had no effect on the patient's symptoms, hypoxemia and lung function, suggesting bronchiolitis associated with inhalation of hard metal.

Recent developments in human biomonitoring: non-invasive assessment of target tissue dose and effects of pneumotoxic metals.

Tobacco smoke and polluted environments substantially increase the lung burden of pneumotoxic chemicals, particularly pneumotoxic metallic elements. To achieve a better understanding of the early events between exposure to inhaled toxicants and the onset of adverse effects on the lung, the characterization of dose at the target organ would be extremely useful. Exhaled breath condensate (EBC), obtained by cooling exhaled air under conditions of spontaneous breathing, is a novel technique that could provide a non-invasive assessment of pulmonary pathobiology. Considering that EBC is water practically free of interfering solutes, it represents an ideal biological matrix for elemental characterization. Published data show that several toxic metals and trace elements are detectable in EBC, raising the possibility of using this medium to quantify the lung tissue dose of pneumotoxic substances. This novel approach may represent a significant advance over the analysis of alternative media (blood, serum, urine, hair), which are not as reliable (owing to interfering substances in the complex matrix) and reflect systemic rather than lung (target tissue) levels of both toxic metals and essential trace elements. Data obtained among workers occupationally exposed to either hard metals or chromium (VI) and in smokers with or without chronic obstructive pulmonary disease (COPD) are reviewed to show that--together with biomarkers of exposure--EBC also allows the simultaneous quantification of biomarkers of effect directly sampled from the epithelial lining fluid, thus providing novel insights on both kinetic and dynamic aspects of metal toxicology.

Oral administration of sodium tungstate improves cardiac performance in streptozotocin-induced diabetic rats.

Normalization of hyperglycemia and hyperlipidemia is an important objective in preventing diabetes-induced cardiac dysfunction. Our study investigated the effects of sodium tungstate on cardiac performance in streptozotocin-induced (STZ) diabetic rats based on its potential antidiabetic and antioxidant activity. Male Wistar rats were made STZ-diabetic and then treated with tungstate in their drinking water for 9 weeks. Body mass, food and fluid intake, plasma glucose, insulin, triglyceride, and free fatty acids levels were measured. At the termination of the study period, an oral glucose tolerance test (OGTT) was performed, and cardiac performance was evaluated using an isolated working heart apparatus. Tungstate-treated STZ-diabetic rats showed a significant reduction in fluid and food intake, plasma glucose, triglycerides, and free fatty acid levels, and improved tolerance to glucose in OGTT, owing to tungstate-mediated enhancement of insulin activity rather than increased insulin levels. Left ventricular pressure development, the rate of contraction (+dP/dT), and the rate of relaxation (-dP/dT) were significantly improved in tungstate-treated diabetic rats. Apart from a decreased rate of body mass gain, no other signs of toxicity or hypoglycemic episodes were observed in tungstate-treated rats. This study extends previous observations on the antidiabetic activities of tungstate, and also reports for the first time the salutary effects in preventing diabetic cardiomyopathy.

Tungstate is an effective antidiabetic agent in streptozotocin-induced diabetic rats: a long-term study.

AIMS/HYPOTHESIS: Recent studies have shown the anti diabetic effects of oral sodium tungstate treatment in several animal models of diabetes based on short-term experiments. In this study, we examined the effectiveness of long-term tungstate treatment of streptozotocin-induced-diabetic rats. METHODS: Tungstate was administered to the drinking water of rats for eight months. RESULTS: The treatment resulted in a reduction in serum glucose concentrations in diabetic rats, but no change in glycaemia was detected in healthy rats. Alterations in the hepatic glucose metabolism due to diabetes were almost completely counteracted by tungstate treatment. The partial recovery of glucokinase activity, not found in diabetic animals, normalised glycogen and glucose 6-phosphate concentrations. Tungstate treatment also restored pyruvate kinase activity and fructose 2,6-bisphosphate concentrations. In healthy rats, tungstate treatment did not modify the majority of the hepatic parameters studied. Moreover, tungstate treatment prevented diabetes-induced morphological changes in the kidney and ocular lens and also reduced mortality. Furthermore, no hypoglycaemic episodes or undesirable side effects were observed in treated diabetic or healthy rats. In addition, there is no evidence of intolerance developing after prolonged use. CONCLUSION/INTERPRETATION: Tungstate could play a helpful part in the long-term treatment of diabetes.