Nasal and Pulmonary Toxicity of Titanium Dioxide Nanoparticles in Rats

In recent decades, titanium dioxide (TiO2) nanoparticles have been used in various applications, including paints, coatings, and food. However, data are lacking on the toxicological aspects associated with their use. The aim of this study was to assess the inhalation toxicity of TiO2 nanoparticles in rats by using inhalation exposure. Male Wistar rats were exposed to TiO2 nanoparticles for 2 weeks (6 hr/day, 5 days/week) at a mean mass concentration of 11.39 +/- 0.31 mg/m3. We performed time-course necropsies at 1, 7, and 15 days after exposure. Lung inflammation and injury were assessed on the basis of the total and individual cell counts in bronchoalveolar lavage fluid (BALF), and by biochemical assays, including an assay for lactate dehydrogenase (LDH). Furthermore, histopathological examination was performed to investigate the lungs and nasal cavity of rats. There were no statistically significant changes in the number of BALF cells, results of biochemical assays of BALF and serum, and results of cytokine analysis. However, we did observe histopathological changes in the nasal cavity tissue. Lesions were observed at post-exposure days 1 and 7, which resolved at post-exposure day 15. We also calculated the actual amounts of TiO2 nanoparticles inhaled by the rats. The results showed that the degree of toxicity induced by TiO2 nanoparticles correlated with the delivered quantities. In particular, exposure to small particles with a size of approximately 20 nm resulted in toxicity, even if the total particle number was relatively low.

The Incidence Rate and Severity of Orthotopic Lung Cancer in an Animal Model Depends on the Number of A549 Cells and Transplantation Period / 한국실험동물학회지

The incidence rate of lung cancer is continually increasing, and lung cancer is the leading cause of cancer-related death worldwide. Nevertheless, few therapeutic methods are available for lung cancer. Therefore, establishing appropriate lung cancer animal models is important to investigate mechanisms and to evaluate new drugs for lung cancer. In the present study, we transplanted non-small cell lung cancer A549 human adenocarcinoma cells (2x10(4), 2.0x10(5), and 2.0x10(6) cells) into the right lobe of BALB/c nude mice via the intercostal space to develop an orthotopic lung cancer animal model that is minimally invasive and similar to human lung cancer. We then investigated the incidence rate and severity of lung cancer according to the A549 cell number (2x10(4), 2.0x10(5), and 2.0x10(6) cells) and transplantation periods (4~23 days). Lung cancer development was confirmed with gross examination, which was supported by histopathological examination. These results indicate that the incidence rate and severity of lung cancer was increased depending on the number of transplanted cells and transplantation period which the cell number and duration are increasing risk of lung cancer. Thus, this study can provide appropriate reference data to develop an orthotopic lung cancer animal model using the non-small cell lung cancer A549 cell line for researching mechanisms and evaluating candidate drugs, including various approaches for treating lung cancer.

Point Mutation of Hoxd12 in Mice

PURPOSE: Genes of the HoxD cluster play a major role in vertebrate limb development, and changes that modify the Hoxd12 locus affect other genes also, suggesting that HoxD function is coordinated by a control mechanism involving multiple genes during limb morphogenesis. In this study, mutant phenotypes were produced by treatment of mice with a chemical mutagen, N-ethyl-N-nitrosourea (ENU). We analyzed mutant mice exhibiting the specific microdactyly phenotype and examined the genes affected. MATERIALS AND METHODS: We focused on phenotype characteristics including size, bone formation, and digit morphology of ENU-induced microdactyly mice. The expressions of several molecules were analyzed by genome-wide screening and quantitative real-time PCR to define the affected genes. RESULTS: We report on limb phenotypes of an ENU-induced A-to-C mutation in the Hoxd12 gene, resulting in alanine-to-serine conversion. Microdactyly mice exhibited growth defects in the zeugopod and autopod, shortening of digits, a missing tip of digit I, limb growth affected, and dramatic increases in the expressions of Fgf4 and Lmx1b. However, the expression level of Shh was not changed in Hoxd12 point mutated mice. CONCLUSION: These results suggest that point mutation rather than the entire deletion of Hoxd12, such as in knockout and transgenic mice, causes the abnormal limb phenotype in microdactyly mice. The precise nature of the spectrum of differences requires further investigation.

Clinical Analysis of Primary Hyperparathyroidism / 대한내분비외과학회지

Primary hyperparathyroidism is a rare disease that can be accurately diagnosed and effectively treated in most patients. The diagnosis is established by a persistent elevation of serum calcium and parathyroid hormone and by clinical evaluation. With the introduction of a biochemical screening test for calcium and the development of radiologic techniques, the detection of hyperparathyroidism has increased slightly. However, the parathyroidectomy is still not a common operation in Korea. Twenty-eight patients with primary hyperparathyroidism comprised of 14 males and 14 females, were treated by operation from January 1986 to December 1995 at Kyunghee University Hospital and the data were analyzed retrospectively. The results are as follows: 1) The sex distribution was 14 males & 14 females, and the age distribution was from 14 to 79 years. 2) The clincal manifestations were renal symptoms (42.9%), skeletal symptoms (28.6%), a neck mass (10.7%), pancreatitis (7.1%) , no symptoms (7.1%), polydipsia (3.6%) in order of frequency. 3) Most of the patients showed hypercalcemia above 11mg/dl, but five patients had calcium levels which were either slightly increased or in the upper normal range. 4) The preoperative localization methods were mainly combinations of sonography, C.T.,and Tl-Tc subtraction scans and showed high sensitivity & specificity (above 90%). 5) The main tumor locations were the Rt. lower pole in 10 cases, the Rt. upper pole in 5 cases, the Lt. upper pole in 3 cases, the Lt. lower pole in 7 cases; there were 2 cases of ectopic location and 1 case of hyperplasia at the Rt. upper & the Lt. lower pole. 6) The pathologic findings revealed a solitary adenoma in 25 patients, a carcinoma in two patients, and hyperplasia associated with MEN2a in 1 patient. 7) We experienced one case of recurrence after primary excision at the Rt. lower pole. Reoperation for a missed gland, after the primary operation, was performed in one patient; the excision of the tumor was performed successsfully. 8) We performed surgical excisions and 17 patients showed hypocalcemia postoperatively. Most of the hypocalcemia was transient and disappeared after ingestion of oral calcium agents or usuage of Vit. D3.