Some of the rare earth elements such as Sc are believed to be non-toxic and, at present, are widely utilized for the replacement of toxic heavy metals in technological applications, but they are not entirely free of toxicity, with hidden potential health risks. In this animal experiment, we report the urinary scandium (Sc) excretion rate and nephrotoxiciy in male Wistar rats. For this purpose, the rats were given a single dose of a solution of scandium chloride by intraperitoneal injection. The Sc excretion (U-Sc) was determined in 24-h urine samples by inductively coupled plasma-argon emission spectrometry along with the Sc nephrotoxicity, urine volume (UV), creatinine (Crt), beta-2-microglobulin (beta2-MG) and N-acetyl-beta-D-glucosaminidase (NAG). A dose-dependent Sc excretion of 0.0063% (r = 0.97) via 24-h urine was confirmed. The administration of Sc induced a significant decrease of UV and Crt and a significant increase of NAG and beta2-MG. These results suggest that U-Sc can be a useful tool for monitoring Sc exposure. The formation of Sc colloidal conjugates that deposit in glomeruli may be the cause of a reduction of the glomerular filtration rate. We propose that the analytical method and results described in this study will be of great importance for future toxicological studies on Sc exposure.

As fluoride has a very short half-life in the body and the major route for fluoride excretion is via the kidney, human exposure is best measured in urine, where the concentration is expected to be highest. The urinary fluoride concentrations of 167 healthy Japanese adults were determined by means of a fluoride ion selective electrode. When the results were corrected for a specific gravity rho = 1.024 g cm-3, the histogram of urinary fluoride concentrations highly skewed toward low values with sharp peakedness (skewness = 1.56, kurtosis = 3.08). The normality of the log-transformed histogram (skewness = 0.12, kurtosis = 0.07) and the straight line on log-probability paper clearly showed a key feature of lognormal distribution of urinary fluoride. A geometric mean (GM) of 613.8 microg/l and 95% confidential interval (CI) of 241.0-1633.1 microg/l were established as reference values for urinary fluoride. The results presented in this study will be useful as guidelines for the biological monitoring of fluoride in normal subjects and individuals at risk of occupational or environmental fluoride exposure.

In our previous study, we reported that even a sublethal dose of hydrofluoric acid (HFA) could cause acute toxic effects 60 min after intravenous injection. This study was designed to investigate the time-and dosedependent changes associated with these disorders. The serum fluoride (F) kinetics are also considered in the discussion of the relationship between the concentrations of serum F and the disorders. Methods: Rats were injected with HFA (1.6 or 9.6 mg/kg body weight) for the dose-response relationship study. For each dose, the rats were assigned to one of seven groups. Blood samples of the 0-min group were obtained from the carotid artery prior to injection as a control. The other six groups were labeled according to sampling times (5, 10, 30, 60, 120 and 300-min) in the time-dependent study. Results: The 1.6 mg/kg dose decreased the ionized calcium (Ca 2+ ) level significantly after 30 min, and it also decreased the total calcium (Ca) level after 300 min. The 9.6 mg/kg dose rapidly worsened renal dysfunction after 60 min. It increased the serum potassium level after 60 and 120 min and it decreased Ca and Ca 2+ levels until 300 min. Although there was respiratory compensation, the base excess and HCO 3 -level and had not completely recovered by 300 min. Conclusions: Even low exposure to HFA caused renal dysfunction, and electrolyte abnormalities and metabolic acidosis lasted for several hours in rats. Therefore, persons involved in HFA accidental exposure should be closely monitored over time, even if the exposure is less than the sublethal dose. (J Occup Health 2009; 51: 287-293)

Background: For epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), administration of EGFR tyrosine kinase inhibitors (TKIs) is mandatory to prolong survival. To date, a comparison of second-and third-generation EGFR-TKIs has not been reported as far as we are aware. Patients and Methods: We retrospectively investigated the survival time of patients diagnosed with EGFR-mutated advanced or recurrent NSCLC who had received afatinib, a second-generation EGFR-TKI, or osimertinib, a third-generation EGFR-TKI, as the first-line treatment. Results: Among the 49 patients included in the study, 15 received afatinib and 34 received osimertinib. No significant differences in overall survival were observed between the two groups [afatinib vs. osimertinib=36 vs. 33 months (hazard ratio=2.917, 95% confidence interval=0.780-10.905; p=0.112)]. T790M mutation was detected in three of the patients in the afatinib group, and all three subsequently received osimertinib. The median overall survival of these three patients and of the 12 without the mutation were 63 and 36 months, respectively. Conclusion: There was no apparent difference in the effect on survival between second-and thirdgeneration EGFR-TKIs, whereas the sequential administration of second-followed by third-generation EGFR-TKIs appeared to confer a better long-term prognosis.Mutations in the epidermal growth factor receptor (EGFR) gene are important drivers of non-small-cell lung cancer (NSCLC). For EGFR mutation-positive NSCLC, administration of EGFR tyrosine kinase inhibitors (TKIs) remains crucial for prolonging survival. Currently approved EGFR-TKIs include firstgeneration gefitinib and erlotinib, second-generation afatinib and dacomitinib, and third-generation osimertinib.Afatinib is an oral, irreversible blocker of the ERB-B2 receptor tyrosine kinase family of EGFR, EGFR2 (HER2⁄ERBB2), ERBB3, and ERBB4 signaling factors (1, 2). Afatinib demonstrated superior progression-free survival (PFS) in the LUX-Lung-7 trial, a comparative study with the first-generation EGFR-TKI gefitinib, and has been approved as first-line treatment for EGFR mutation-positive NSCLC (3). Although no statistical superiority was observed in terms of overall survival (OS), the median OS was longer following afatinib treatment (4). Subgroup analysis revealed that afatinib tended to afford better OS in patients with exon 19 deletion and patients with L858R mutation. Furthermore, both non-Asian and Asian patients tended to demonstrate better OS following afatinib therapy. Afatinib can be administered in any treatment line. Furthermore, the T790M EGFR mutation is a mechanism of resistance to afatinib (5), and in those cases, sequential administration of osimertinib may be expected to further prolong OS.Osimertinib is a third-generation, irreversible, oral EGFR-TKI that selectively inhibits tumors with TKI-sensitizing and T790M resistance-associated EGFR mutations (6, 7). Osimertinib reportedly afforded superior PFS in the FLAURA trial, a comparative study of first...

We report a rare case of large cell neuroendocrine carcinoma (LCNEC) of the lung with cancer-associated retinopathy (CAR). To our knowledge, only two cases of LCNEC with CAR have been reported, one in 1995 and another in 2013. CAR, typically associated with small cell lung cancer (SCLC), is one of the paraneoplastic syndromes with deterioration of visual acuity, visual field constriction, and photophobia. CAR is caused by an autoimmune system reaction against the same antigen in the tumor and retinal photoreceptor cells. To diagnose CAR, genetic retinal dystrophies or any other medical causes of retinopathy should be excluded, but there are no standard diagnostic criteria. Anti-retinal antibodies are known to be positive in CAR patients, and anti-recoverin antibodies are thought to be sensitive and specific to CAR. In our case, anti-recoverin antibodies were not detected by serum tests, but CAR could be diagnosed on the basis of ophthalmological findings including clinical symptoms, electroretinographic findings, and visual field tests. CAR with clinical features of rapid visual disorder should be considered in LCNEC patients as well as in SCLC patients.