Tissue distribution of manganese in iron-sufficient or iron-deficient rats after stainless steel welding-fume exposure.

Welders can be exposed to high levels of manganese through welding fumes. Although it has already been suggested that excessive manganese exposure causes neurotoxicity, called manganism, the pathway of manganese transport to the brain with welding-fume exposure remains unclear. Iron is an essential metal that maintains a homeostasis in the body. The divalent metal transporter 1 (DMT1) transports iron and other divalent metals, such as manganese, and the depletion of iron is known to upregulate DMT1 expression. Accordingly, this study investigated the tissue distribution of manganese in iron-sufficient and iron-deficient rats after welding-fume exposure. The feeding of an iron-deficient diet for 4 wk produced a depletion of body iron, such as decreased iron levels in the serum and tissues, and upregulated the DMT1 expression in the rat duodenum. The iron-sufficient and iron-deficient rats were then exposed to welding fumes generated from manual metal arc stainless steel at a concentration of 63.5 +/- 2.3 mg/m3 for 2 h per day over a 30-day period. Animals were sacrificed on days 1, 15, and 30. The level of body iron in the iron-deficient rats was restored to the control level after the welding-fume exposure. However, the tissue distributions of manganese after the welding-fume exposure showed similar patterns in both the iron-sufficient and iron-deficient groups. The concentration of manganese increased in the lungs and liver on days 15 and 30, and increased in the olfactory bulb on day 30. Slight and heterogeneous increases of manganese were observed in different brain regions. Consequently, these findings suggest that the presence of Fe in the inhaled welding fumes may not have a significant effect on the uptake of Mn into the brain. Thus, the condition of iron deficiency did not seem to have any apparent effect on the transport of Mn into the brain after the inhalation of welding fumes.

Changes in blood manganese concentration and MRI t1 relaxation time during 180 days of stainless steel welding-fume exposure in cynomolgus monkeys.

Welders are at risk of being exposed to high concentrations of welding fumes and developing pneumoconiosis or other welding-fume exposure-related diseases. Among such diseases, manganism resulting from welding-fume exposure remains a controversial issue, as although the movement of manganese into specific brain regions has been established, the similar movement of manganese presented with other metals, such as welding fumes, has not been clearly demonstrated as being similar to that of manganese alone. Meanwhile, the competition between Mn and iron for iron transporters, such as transferrin and DMT-1, to the brain has also been implicated in the welding-fume exposure. Thus, the increased signal intensities in the basal ganglia, including the globus pallidus and subcortical frontal white matter, based on T1-weighted magnetic resonances in welders, require further examination as regards the correspondence with an increased manganese concentration. Accordingly, to investigate the movement of manganese after welding-fume exposure, 6 cynomolgus monkeys were acclimated for 1 mo and assigned to 3 dose groups: unexposed, low dose of (total suspended particulate [TSP] 31 mg/m3, 0.9 mg/m3 of Mn), and high dose of total suspended particulate (62 mg/m3 TSP, 1.95 mg/m3 of Mn). The primates were exposed to manual metal-arc stainless steel (MMA-SS) welding fumes for 2 h/day in an inhalation chamber system equipped with an automatic fume generator for 6 mo. Magnetic resonance imaging (MRI) studies of the basal ganglia were conducted before the initiation of exposure and thereafter every month. During the exposure, the blood chemistry was monitored every 2 wk and the concentrations of metal components in the blood were measured every 2 wk and compared with ambient manganese concentrations. The manganese concentrations in the blood did not show any significant increase until after 2 mo of exposure, and then reached a plateau after 90 days of exposure, showing that an exposure period of at least 60 days was required to build up the blood Mn concentration. Furthermore, as the blood Mn concentration continued to build, a continued decrease in the MRI T1 relaxation time in the basal ganglia was also detected. These data suggested that prolonged inhalation of welding fumes induces a high MRI T1 signal intensity with an elevation of the blood manganese level. The presence of a certain amount of iron or other metals, such as Cr and Ni, in the inhaled welding fumes via inhalation was not found to have a significant effect on the uptake of Mn into the brain or the induction of a high MRI T1 signal intensity.

Comparison of high MRI T1 signals with manganese concentration in brains of cynomolgus monkeys after 8 months of stainless steel welding-fume exposure.

Several pharmacokinetic studies on inhalation exposure to manganese (Mn) have already demonstrated that Mn readily accumulates in the olfactory and brain regions. However, a shortening of the magnetic resonance imaging (MRI) T1 relaxation time or high T1 signal intensity in specific sites of the brain, including the globus pallidus and subcortical frontal white matter, as indicative of tissue manganese accumulation has not yet been clearly established for certain durations of known doses of welding-fume exposure in experimental animals. Accordingly, to investigate the movement of manganese after welding-fume exposure, six cynomolgus monkeys were acclimated and assigned to three dose groups: unexposed, low dose (31 mg/m(3) total suspended particulate [TSP], 0.9 mg/m(3) of Mn), and high dose (62 mg/m(3) TSP, 1.95 mg/m(3) of Mn) of total suspended particulate. The primates were exposed to manual metal arc stainless steel (MMA-SS) welding fumes for 2 h per day in an inhalation chamber system equipped with an automatic fume generator. Magnetic resonance imaging (MRI) studies were conducted before the initiation of exposure and thereafter every month. The tissue Mn concentrations were then measured after a plateau was reached regarding the shortening of the MRI T1 relaxation time. A dose-dependent increase in the Mn concentration was found in the lungs, while noticeable increases in the Mn concentrations were found in certain tissues, such as the liver, kidneys, and testes. Slight increases in the Mn concentrations were found in the caudate, putamen, frontal lobe, and substantia nigra, while a dose-dependent noticeable increase was only found in the globus pallidus. Therefore, the present results indicated that a shortening of the MRI T1 relaxation time corresponded well with the Mn concentration in the globus pallidus after prolonged welding-fume exposure.

Clinicopathologic review of pulmonary silicone embolism with special emphasis on the resultant histologic diversity in the lung--a review of five cases.

It is known that the subcutaneous injection of silicone can lead to severe pulmonary complications, followed in some patients by respiratory failure. Currently, silicone is being increasingly applied in the field of plastic surgery and, unfortunately, the illicit injection of silicone fluid by uncertified practitioners is not uncommon in Korea. We offer a critical pathologic review of 5 cases of pulmonary silicone embolism following illegal injection to the vaginal wall, four of which were fatal and came to legal autopsy. Our findings again confirm that subcutaneously injected silicone can gain access to the pulmonary vascular tree and cause pulmonary embolism. The histologic changes observed in the lung are variable and include four patterns i.e., the mere presence of silicone emboli, congestion and hemorrhage, acute pneumonitis, and diffuse alveolar damage despite the severe critical course in all cases. We were unable to find any histologic pattern that correlates well with the clinical course. Apart from producing emboli in the pulmonary vessels, subcutaneous injection of silicone can obviously cause serious pulmonary disease due to its ability to induce acute to induce acute pneumonitis and even possibly acute respiratory distress syndrome.