The Experts below are selected from a list of 285 Experts worldwide ranked by ideXlab platform
Greg A. Krempl - One of the best experts on this subject based on the ideXlab platform.
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S173 – Ectopic Intratracheal Thyroid Cancer
Otolaryngology-Head and Neck Surgery, 2008Co-Authors: James Travis Brawner, Greg A. KremplAbstract:Objectives1) To describe a case of ectopic Intratracheal thyroid cancer. 2) To review the literature describing ectopic Intratracheal thyroid tissue.MethodsEctopic thyroid tissue is periodically encountered and can sometimes be malignant. The most common locations for ectopic thyroid tissue to be found are the tongue and along the tract of descent of the thyroid gland into the neck. We describe a case of ectopic Intratracheal thyroid cancer and review the literature for similar cases. We also discuss possible explanations for this phenomenon.ResultsA total thyroidectomy with tracheal resection was performed. The patient received postoperative I131 therapy and has no detectable serum thyroglobulin to date. There is a small number of cases that report ectopic thyroid tissue found in the trachea. 3 of these were malignant. Including the current case, 26% of ectopic Intratracheal tissue is malignant.ConclusionsEctopic Intratracheal thyroid tissue is rare. Since 26% of reported cases have been malignant, we su...
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S173 – Ectopic Intratracheal Thyroid Cancer
Otolaryngology–Head and Neck Surgery, 2008Co-Authors: James Travis Brawner, Greg A. KremplAbstract:Objectives 1) To describe a case of ectopic Intratracheal thyroid cancer. 2) To review the literature describing ectopic Intratracheal thyroid tissue. Methods Ectopic thyroid tissue is periodically encountered and can sometimes be malignant. The most common locations for ectopic thyroid tissue to be found are the tongue and along the tract of descent of the thyroid gland into the neck. We describe a case of ectopic Intratracheal thyroid cancer and review the literature for similar cases. We also discuss possible explanations for this phenomenon. Results A total thyroidectomy with tracheal resection was performed. The patient received postoperative I131 therapy and has no detectable serum thyroglobulin to date. There is a small number of cases that report ectopic thyroid tissue found in the trachea. 3 of these were malignant. Including the current case, 26% of ectopic Intratracheal tissue is malignant. Conclusions Ectopic Intratracheal thyroid tissue is rare. Since 26% of reported cases have been malignant, we suggest that resection is the appropriate therapy, as opposed to the alternative endoscopic laser debulking.
Yasuo Morimoto - One of the best experts on this subject based on the ideXlab platform.
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Comparison of Responses in Rat Lung Following Inhalation and Intratracheal Administration of Nanoparticles
Current Topics in Environmental Health and Preventive Medicine, 2019Co-Authors: Yukiko Yoshiura, Takako Oyabu, Hiroto Izumi, Taisuke Tomonaga, Toshihiko Myojo, Yuri Fujisawa, Masaru Kubo, Manabu Shimada, Yasuo MorimotoAbstract:We compared the concentration of total protein in bronchoalveolar lavage fluid (BALF) exposed to four types of nanomaterials in an inhalation study and in an Intratracheal instillation study in order to examine whether the ranking of the harmful effect of nanomaterials following Intratracheal instillation accorded with the ranking following inhalation. We used nickel oxide (NiO) nanoparticles and cerium dioxide (CeO2) nanoparticles as high toxicity nanomaterials, and titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles as low toxicity nanomaterials. In the inhalation study, rats were exposed to approximately 2 mg/m3 of four nanomaterials for 4 weeks, and the total protein concentrations in the bronchoalveolar lavage fluid (BALF) were examined from 3 days to 3 months after the end of exposure as the endpoint of pulmonary toxicity. In the Intratracheal instillation study, rats were exposed to 0.2 or 1 mg of four nanomaterials, and, with the same endpoint, the BALF was analyzed from 3 days to 6 months after the exposure. The inhalation of NiO and CeO2, the high toxicity nanomaterials, induced a significant amount of total protein in the BALF, while the inhalation of ZnO and TiO2, the low toxicity nanomaterials, did not. The Intratracheal instillation of NiO and CeO2 resulted in a persistently elevated concentration of total protein in the BALF, while the same result with the Intratracheal instillation of ZnO and TiO2 was transient. Taken together, a difference in concentration of total protein in BALF was observed between the high and low toxicity nanomaterials following Intratracheal instillation as well as inhalation, suggesting that the ranking of the harmful effects of nanoparticles in Intratracheal instillation studies may reflect the ranking in inhalation studies.
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Basic study of Intratracheal instillation study of nanomaterials for the estimation of the hazards of nanomaterials.
Industrial health, 2017Co-Authors: Yasuo Morimoto, Hiroto Izumi, Yukiko Yoshiura, Kazuhiro Yatera, Yuri Fujisawa, Katsuhide Fujita, Junko Maru, Shigehisa Endoh, Kazumasa HondaAbstract:In order to examine the usefulness of Intratracheal instillation of nanoparticles for the screening of the harmful effects of nanoparticles, we performed Intratracheal instillation studies of nanomaterials on rats using different delivery devices and postures as a basic study. Multiwall carbon nanotubes (MWCNTs) with a geometric mean length and secondary diameter of 2.16 μm and 752 nm, respectively, were used as the nanomaterials. Male F344 rats were Intratracheally exposed to 0.04 or 0.2 mg/rat of MWCNT, were dissected at 1 d and 3 d, and cell analyses of the bronchoalveolar lavage fluid (BALF) were analyzed. Two delivery devices were used for the Intratracheal instillation of the MWCNTs: a gavage needle and a microsprayer aerolizer. Both induced neutrophil influx in the lung at 1 and 3 d, and there were no significant differences in neutrophil inflammation between the two delivery devices. The main distribution of pulmonary inflammation by both delivery devices was in the centrilobular spaces in the lung. Two postures were used: an angle of approximately 45 degrees and a standing posture on a board, both of which also induced pulmonary influx in BALF and pulmonary inflammation mainly in the centrilobular spaces, with no large difference in pulmonary inflammation between the two postures. Taken together, the differences in the delivery devices and postures of the rats in the Intratracheal instillation did not affect the acute pulmonary toxicity of the nanomaterials.
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Significance of Intratracheal Instillation Tests for the Screening of Pulmonary Toxicity of Nanomaterials.
Journal of UOEH, 2017Co-Authors: Yasuo Morimoto, Hiroto Izumi, Yukiko Yoshiura, Yuri Fujisawa, Katsuhide FujitaAbstract:Inhalation tests are the gold standard test for the estimation of the pulmonary toxicity of respirable materials. Intratracheal instillation tests have been used widely, but they yield limited evidence of the harmful effects of respirable materials. We reviewed the effectiveness of Intratracheal instillation tests for estimating the hazards of nanomaterials, mainly using research papers featuring Intratracheal instillation and inhalation tests centered on a Japanese national project. Compared to inhalation tests, Intratracheal instillation tests induced more acute inflammatory responses in the animal lung due to a bolus effect regardless of the toxicity of the nanomaterials. However, nanomaterials with high toxicity induced persistent inflammation in the chronic phase, and nanomaterials with low toxicity induced only transient inflammation. Therefore, in order to estimate the harmful effects of a nanomaterial, an observation period of 3 months or 6 months following Intratracheal instillation is necessary. Among the endpoints of pulmonary toxicity, cell count and percentage of neutrophil, chemokines for neutrophils and macrophages, and oxidative stress markers are considered most important. These markers show persistent and transient responses in the lung from nanomaterials with high and low toxicity, respectively. If the evaluation of the pulmonary toxicity of nanomaterials is performed in not only the acute but also the chronic phase in order to avoid the bolus effect of Intratracheal instillation and inflammatory-related factors that are used as endpoints of pulmonary toxicity, we speculate that Intratracheal instillation tests can be useful for screening for the identification of the hazard of nanomaterials through pulmonary inflammation.
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evaluation of pulmonary toxicity of zinc oxide nanoparticles following inhalation and Intratracheal instillation
International Journal of Molecular Sciences, 2016Co-Authors: Yasuo Morimoto, Takako Oyabu, Hiroto Izumi, Yukiko Yoshiura, Kazuhiro Yatera, Taisuke Tomonaga, Toshihiko Myojo, Kazuaki Kawai, Manabu Shimada, Masaru KuboAbstract:We conducted inhalation and Intratracheal instillation studies of zinc oxide (ZnO) nanoparticles in order to examine their pulmonary toxicity. F344 rats were received Intratracheal instillation at 0.2 or 1 mg of ZnO nanoparticles with a primary diameter of 35 nm that were well-dispersed in distilled water. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed at three days, one week, one month, three months, and six months after the instillation. As the inhalation study, rats were exposed to a concentration of inhaled ZnO nanoparticles (2 and 10 mg/m3) for four weeks (6 h/day, 5 days/week). The same endpoints as in the Intratracheal instillation study were analyzed at three days, one month, and three months after the end of the exposure. In the Intratracheal instillation study, both the 0.2 and the 1.0 mg ZnO groups had a transient increase in the total cell and neutrophil count in the BALF and in the expression of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in the BALF. In the inhalation study, transient increases in total cell and neutrophil count, CINC-1,-2 and HO-1 in the BALF were observed in the high concentration groups. Neither of the studies of ZnO nanoparticles showed persistent inflammation in the rat lung, suggesting that well-dispersed ZnO nanoparticles have low toxicity.
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Usefulness of Intratracheal Instillation Studies for Estimating Nanoparticle-Induced Pulmonary Toxicity
International journal of molecular sciences, 2016Co-Authors: Yasuo Morimoto, Hiroto Izumi, Yukiko Yoshiura, Kei Fujishima, Kazuhiro Yatera, Kazuhiro YamamotoAbstract:Inhalation studies are the gold standard for the estimation of the harmful effects of respirable chemical substances, while there is limited evidence of the harmful effects of chemical substances by Intratracheal instillation. We reviewed the effectiveness of Intratracheal instillation studies for estimating the hazards of nanoparticles, mainly using papers in which both inhalation and Intratracheal instillation studies were performed using the same nanoparticles. Compared to inhalation studies, there is a tendency in Intratracheal instillation studies that pulmonary inflammation lasted longer in the lungs. A difference in pulmonary inflammation between high and low toxicity nanoparticles was observed in the Intratracheal instillation studies, as in the inhalation studies. Among the endpoints of pulmonary toxicity, the kinetics of neutrophil counts, percentage of neutrophils, and chemokines for neutrophils and macrophages, heme oxygenase-1 (HO-1) in bronchoalveolar lavage fluid (BALF), reflected pulmonary inflammation, suggesting that these markers may be considered the predictive markers of pulmonary toxicity in both types of study. When comparing pulmonary inflammation between Intratracheal instillation and inhalation studies under the same initial lung burden, there is a tendency that the inflammatory response following the Intratracheal instillation of nanoparticles is greater than or equal to that following the inhalation of nanoparticles. If the difference in clearance in both studies is not large, the estimations of pulmonary toxicity are close. We suggest that Intratracheal instillation studies can be useful for ranking the hazard of nanoparticles through pulmonary inflammation.
James Travis Brawner - One of the best experts on this subject based on the ideXlab platform.
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S173 – Ectopic Intratracheal Thyroid Cancer
Otolaryngology-Head and Neck Surgery, 2008Co-Authors: James Travis Brawner, Greg A. KremplAbstract:Objectives1) To describe a case of ectopic Intratracheal thyroid cancer. 2) To review the literature describing ectopic Intratracheal thyroid tissue.MethodsEctopic thyroid tissue is periodically encountered and can sometimes be malignant. The most common locations for ectopic thyroid tissue to be found are the tongue and along the tract of descent of the thyroid gland into the neck. We describe a case of ectopic Intratracheal thyroid cancer and review the literature for similar cases. We also discuss possible explanations for this phenomenon.ResultsA total thyroidectomy with tracheal resection was performed. The patient received postoperative I131 therapy and has no detectable serum thyroglobulin to date. There is a small number of cases that report ectopic thyroid tissue found in the trachea. 3 of these were malignant. Including the current case, 26% of ectopic Intratracheal tissue is malignant.ConclusionsEctopic Intratracheal thyroid tissue is rare. Since 26% of reported cases have been malignant, we su...
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S173 – Ectopic Intratracheal Thyroid Cancer
Otolaryngology–Head and Neck Surgery, 2008Co-Authors: James Travis Brawner, Greg A. KremplAbstract:Objectives 1) To describe a case of ectopic Intratracheal thyroid cancer. 2) To review the literature describing ectopic Intratracheal thyroid tissue. Methods Ectopic thyroid tissue is periodically encountered and can sometimes be malignant. The most common locations for ectopic thyroid tissue to be found are the tongue and along the tract of descent of the thyroid gland into the neck. We describe a case of ectopic Intratracheal thyroid cancer and review the literature for similar cases. We also discuss possible explanations for this phenomenon. Results A total thyroidectomy with tracheal resection was performed. The patient received postoperative I131 therapy and has no detectable serum thyroglobulin to date. There is a small number of cases that report ectopic thyroid tissue found in the trachea. 3 of these were malignant. Including the current case, 26% of ectopic Intratracheal tissue is malignant. Conclusions Ectopic Intratracheal thyroid tissue is rare. Since 26% of reported cases have been malignant, we suggest that resection is the appropriate therapy, as opposed to the alternative endoscopic laser debulking.
Yukiko Yoshiura - One of the best experts on this subject based on the ideXlab platform.
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Comparison of Responses in Rat Lung Following Inhalation and Intratracheal Administration of Nanoparticles
Current Topics in Environmental Health and Preventive Medicine, 2019Co-Authors: Yukiko Yoshiura, Takako Oyabu, Hiroto Izumi, Taisuke Tomonaga, Toshihiko Myojo, Yuri Fujisawa, Masaru Kubo, Manabu Shimada, Yasuo MorimotoAbstract:We compared the concentration of total protein in bronchoalveolar lavage fluid (BALF) exposed to four types of nanomaterials in an inhalation study and in an Intratracheal instillation study in order to examine whether the ranking of the harmful effect of nanomaterials following Intratracheal instillation accorded with the ranking following inhalation. We used nickel oxide (NiO) nanoparticles and cerium dioxide (CeO2) nanoparticles as high toxicity nanomaterials, and titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles as low toxicity nanomaterials. In the inhalation study, rats were exposed to approximately 2 mg/m3 of four nanomaterials for 4 weeks, and the total protein concentrations in the bronchoalveolar lavage fluid (BALF) were examined from 3 days to 3 months after the end of exposure as the endpoint of pulmonary toxicity. In the Intratracheal instillation study, rats were exposed to 0.2 or 1 mg of four nanomaterials, and, with the same endpoint, the BALF was analyzed from 3 days to 6 months after the exposure. The inhalation of NiO and CeO2, the high toxicity nanomaterials, induced a significant amount of total protein in the BALF, while the inhalation of ZnO and TiO2, the low toxicity nanomaterials, did not. The Intratracheal instillation of NiO and CeO2 resulted in a persistently elevated concentration of total protein in the BALF, while the same result with the Intratracheal instillation of ZnO and TiO2 was transient. Taken together, a difference in concentration of total protein in BALF was observed between the high and low toxicity nanomaterials following Intratracheal instillation as well as inhalation, suggesting that the ranking of the harmful effects of nanoparticles in Intratracheal instillation studies may reflect the ranking in inhalation studies.
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Basic study of Intratracheal instillation study of nanomaterials for the estimation of the hazards of nanomaterials.
Industrial health, 2017Co-Authors: Yasuo Morimoto, Hiroto Izumi, Yukiko Yoshiura, Kazuhiro Yatera, Yuri Fujisawa, Katsuhide Fujita, Junko Maru, Shigehisa Endoh, Kazumasa HondaAbstract:In order to examine the usefulness of Intratracheal instillation of nanoparticles for the screening of the harmful effects of nanoparticles, we performed Intratracheal instillation studies of nanomaterials on rats using different delivery devices and postures as a basic study. Multiwall carbon nanotubes (MWCNTs) with a geometric mean length and secondary diameter of 2.16 μm and 752 nm, respectively, were used as the nanomaterials. Male F344 rats were Intratracheally exposed to 0.04 or 0.2 mg/rat of MWCNT, were dissected at 1 d and 3 d, and cell analyses of the bronchoalveolar lavage fluid (BALF) were analyzed. Two delivery devices were used for the Intratracheal instillation of the MWCNTs: a gavage needle and a microsprayer aerolizer. Both induced neutrophil influx in the lung at 1 and 3 d, and there were no significant differences in neutrophil inflammation between the two delivery devices. The main distribution of pulmonary inflammation by both delivery devices was in the centrilobular spaces in the lung. Two postures were used: an angle of approximately 45 degrees and a standing posture on a board, both of which also induced pulmonary influx in BALF and pulmonary inflammation mainly in the centrilobular spaces, with no large difference in pulmonary inflammation between the two postures. Taken together, the differences in the delivery devices and postures of the rats in the Intratracheal instillation did not affect the acute pulmonary toxicity of the nanomaterials.
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Significance of Intratracheal Instillation Tests for the Screening of Pulmonary Toxicity of Nanomaterials.
Journal of UOEH, 2017Co-Authors: Yasuo Morimoto, Hiroto Izumi, Yukiko Yoshiura, Yuri Fujisawa, Katsuhide FujitaAbstract:Inhalation tests are the gold standard test for the estimation of the pulmonary toxicity of respirable materials. Intratracheal instillation tests have been used widely, but they yield limited evidence of the harmful effects of respirable materials. We reviewed the effectiveness of Intratracheal instillation tests for estimating the hazards of nanomaterials, mainly using research papers featuring Intratracheal instillation and inhalation tests centered on a Japanese national project. Compared to inhalation tests, Intratracheal instillation tests induced more acute inflammatory responses in the animal lung due to a bolus effect regardless of the toxicity of the nanomaterials. However, nanomaterials with high toxicity induced persistent inflammation in the chronic phase, and nanomaterials with low toxicity induced only transient inflammation. Therefore, in order to estimate the harmful effects of a nanomaterial, an observation period of 3 months or 6 months following Intratracheal instillation is necessary. Among the endpoints of pulmonary toxicity, cell count and percentage of neutrophil, chemokines for neutrophils and macrophages, and oxidative stress markers are considered most important. These markers show persistent and transient responses in the lung from nanomaterials with high and low toxicity, respectively. If the evaluation of the pulmonary toxicity of nanomaterials is performed in not only the acute but also the chronic phase in order to avoid the bolus effect of Intratracheal instillation and inflammatory-related factors that are used as endpoints of pulmonary toxicity, we speculate that Intratracheal instillation tests can be useful for screening for the identification of the hazard of nanomaterials through pulmonary inflammation.
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evaluation of pulmonary toxicity of zinc oxide nanoparticles following inhalation and Intratracheal instillation
International Journal of Molecular Sciences, 2016Co-Authors: Yasuo Morimoto, Takako Oyabu, Hiroto Izumi, Yukiko Yoshiura, Kazuhiro Yatera, Taisuke Tomonaga, Toshihiko Myojo, Kazuaki Kawai, Manabu Shimada, Masaru KuboAbstract:We conducted inhalation and Intratracheal instillation studies of zinc oxide (ZnO) nanoparticles in order to examine their pulmonary toxicity. F344 rats were received Intratracheal instillation at 0.2 or 1 mg of ZnO nanoparticles with a primary diameter of 35 nm that were well-dispersed in distilled water. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed at three days, one week, one month, three months, and six months after the instillation. As the inhalation study, rats were exposed to a concentration of inhaled ZnO nanoparticles (2 and 10 mg/m3) for four weeks (6 h/day, 5 days/week). The same endpoints as in the Intratracheal instillation study were analyzed at three days, one month, and three months after the end of the exposure. In the Intratracheal instillation study, both the 0.2 and the 1.0 mg ZnO groups had a transient increase in the total cell and neutrophil count in the BALF and in the expression of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in the BALF. In the inhalation study, transient increases in total cell and neutrophil count, CINC-1,-2 and HO-1 in the BALF were observed in the high concentration groups. Neither of the studies of ZnO nanoparticles showed persistent inflammation in the rat lung, suggesting that well-dispersed ZnO nanoparticles have low toxicity.
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Usefulness of Intratracheal Instillation Studies for Estimating Nanoparticle-Induced Pulmonary Toxicity
International journal of molecular sciences, 2016Co-Authors: Yasuo Morimoto, Hiroto Izumi, Yukiko Yoshiura, Kei Fujishima, Kazuhiro Yatera, Kazuhiro YamamotoAbstract:Inhalation studies are the gold standard for the estimation of the harmful effects of respirable chemical substances, while there is limited evidence of the harmful effects of chemical substances by Intratracheal instillation. We reviewed the effectiveness of Intratracheal instillation studies for estimating the hazards of nanoparticles, mainly using papers in which both inhalation and Intratracheal instillation studies were performed using the same nanoparticles. Compared to inhalation studies, there is a tendency in Intratracheal instillation studies that pulmonary inflammation lasted longer in the lungs. A difference in pulmonary inflammation between high and low toxicity nanoparticles was observed in the Intratracheal instillation studies, as in the inhalation studies. Among the endpoints of pulmonary toxicity, the kinetics of neutrophil counts, percentage of neutrophils, and chemokines for neutrophils and macrophages, heme oxygenase-1 (HO-1) in bronchoalveolar lavage fluid (BALF), reflected pulmonary inflammation, suggesting that these markers may be considered the predictive markers of pulmonary toxicity in both types of study. When comparing pulmonary inflammation between Intratracheal instillation and inhalation studies under the same initial lung burden, there is a tendency that the inflammatory response following the Intratracheal instillation of nanoparticles is greater than or equal to that following the inhalation of nanoparticles. If the difference in clearance in both studies is not large, the estimations of pulmonary toxicity are close. We suggest that Intratracheal instillation studies can be useful for ranking the hazard of nanoparticles through pulmonary inflammation.
Hiroto Izumi - One of the best experts on this subject based on the ideXlab platform.
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Comparison of Responses in Rat Lung Following Inhalation and Intratracheal Administration of Nanoparticles
Current Topics in Environmental Health and Preventive Medicine, 2019Co-Authors: Yukiko Yoshiura, Takako Oyabu, Hiroto Izumi, Taisuke Tomonaga, Toshihiko Myojo, Yuri Fujisawa, Masaru Kubo, Manabu Shimada, Yasuo MorimotoAbstract:We compared the concentration of total protein in bronchoalveolar lavage fluid (BALF) exposed to four types of nanomaterials in an inhalation study and in an Intratracheal instillation study in order to examine whether the ranking of the harmful effect of nanomaterials following Intratracheal instillation accorded with the ranking following inhalation. We used nickel oxide (NiO) nanoparticles and cerium dioxide (CeO2) nanoparticles as high toxicity nanomaterials, and titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles as low toxicity nanomaterials. In the inhalation study, rats were exposed to approximately 2 mg/m3 of four nanomaterials for 4 weeks, and the total protein concentrations in the bronchoalveolar lavage fluid (BALF) were examined from 3 days to 3 months after the end of exposure as the endpoint of pulmonary toxicity. In the Intratracheal instillation study, rats were exposed to 0.2 or 1 mg of four nanomaterials, and, with the same endpoint, the BALF was analyzed from 3 days to 6 months after the exposure. The inhalation of NiO and CeO2, the high toxicity nanomaterials, induced a significant amount of total protein in the BALF, while the inhalation of ZnO and TiO2, the low toxicity nanomaterials, did not. The Intratracheal instillation of NiO and CeO2 resulted in a persistently elevated concentration of total protein in the BALF, while the same result with the Intratracheal instillation of ZnO and TiO2 was transient. Taken together, a difference in concentration of total protein in BALF was observed between the high and low toxicity nanomaterials following Intratracheal instillation as well as inhalation, suggesting that the ranking of the harmful effects of nanoparticles in Intratracheal instillation studies may reflect the ranking in inhalation studies.
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Basic study of Intratracheal instillation study of nanomaterials for the estimation of the hazards of nanomaterials.
Industrial health, 2017Co-Authors: Yasuo Morimoto, Hiroto Izumi, Yukiko Yoshiura, Kazuhiro Yatera, Yuri Fujisawa, Katsuhide Fujita, Junko Maru, Shigehisa Endoh, Kazumasa HondaAbstract:In order to examine the usefulness of Intratracheal instillation of nanoparticles for the screening of the harmful effects of nanoparticles, we performed Intratracheal instillation studies of nanomaterials on rats using different delivery devices and postures as a basic study. Multiwall carbon nanotubes (MWCNTs) with a geometric mean length and secondary diameter of 2.16 μm and 752 nm, respectively, were used as the nanomaterials. Male F344 rats were Intratracheally exposed to 0.04 or 0.2 mg/rat of MWCNT, were dissected at 1 d and 3 d, and cell analyses of the bronchoalveolar lavage fluid (BALF) were analyzed. Two delivery devices were used for the Intratracheal instillation of the MWCNTs: a gavage needle and a microsprayer aerolizer. Both induced neutrophil influx in the lung at 1 and 3 d, and there were no significant differences in neutrophil inflammation between the two delivery devices. The main distribution of pulmonary inflammation by both delivery devices was in the centrilobular spaces in the lung. Two postures were used: an angle of approximately 45 degrees and a standing posture on a board, both of which also induced pulmonary influx in BALF and pulmonary inflammation mainly in the centrilobular spaces, with no large difference in pulmonary inflammation between the two postures. Taken together, the differences in the delivery devices and postures of the rats in the Intratracheal instillation did not affect the acute pulmonary toxicity of the nanomaterials.
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Significance of Intratracheal Instillation Tests for the Screening of Pulmonary Toxicity of Nanomaterials.
Journal of UOEH, 2017Co-Authors: Yasuo Morimoto, Hiroto Izumi, Yukiko Yoshiura, Yuri Fujisawa, Katsuhide FujitaAbstract:Inhalation tests are the gold standard test for the estimation of the pulmonary toxicity of respirable materials. Intratracheal instillation tests have been used widely, but they yield limited evidence of the harmful effects of respirable materials. We reviewed the effectiveness of Intratracheal instillation tests for estimating the hazards of nanomaterials, mainly using research papers featuring Intratracheal instillation and inhalation tests centered on a Japanese national project. Compared to inhalation tests, Intratracheal instillation tests induced more acute inflammatory responses in the animal lung due to a bolus effect regardless of the toxicity of the nanomaterials. However, nanomaterials with high toxicity induced persistent inflammation in the chronic phase, and nanomaterials with low toxicity induced only transient inflammation. Therefore, in order to estimate the harmful effects of a nanomaterial, an observation period of 3 months or 6 months following Intratracheal instillation is necessary. Among the endpoints of pulmonary toxicity, cell count and percentage of neutrophil, chemokines for neutrophils and macrophages, and oxidative stress markers are considered most important. These markers show persistent and transient responses in the lung from nanomaterials with high and low toxicity, respectively. If the evaluation of the pulmonary toxicity of nanomaterials is performed in not only the acute but also the chronic phase in order to avoid the bolus effect of Intratracheal instillation and inflammatory-related factors that are used as endpoints of pulmonary toxicity, we speculate that Intratracheal instillation tests can be useful for screening for the identification of the hazard of nanomaterials through pulmonary inflammation.
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evaluation of pulmonary toxicity of zinc oxide nanoparticles following inhalation and Intratracheal instillation
International Journal of Molecular Sciences, 2016Co-Authors: Yasuo Morimoto, Takako Oyabu, Hiroto Izumi, Yukiko Yoshiura, Kazuhiro Yatera, Taisuke Tomonaga, Toshihiko Myojo, Kazuaki Kawai, Manabu Shimada, Masaru KuboAbstract:We conducted inhalation and Intratracheal instillation studies of zinc oxide (ZnO) nanoparticles in order to examine their pulmonary toxicity. F344 rats were received Intratracheal instillation at 0.2 or 1 mg of ZnO nanoparticles with a primary diameter of 35 nm that were well-dispersed in distilled water. Cell analysis and chemokines in bronchoalveolar lavage fluid (BALF) were analyzed at three days, one week, one month, three months, and six months after the instillation. As the inhalation study, rats were exposed to a concentration of inhaled ZnO nanoparticles (2 and 10 mg/m3) for four weeks (6 h/day, 5 days/week). The same endpoints as in the Intratracheal instillation study were analyzed at three days, one month, and three months after the end of the exposure. In the Intratracheal instillation study, both the 0.2 and the 1.0 mg ZnO groups had a transient increase in the total cell and neutrophil count in the BALF and in the expression of cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-2, chemokine for neutrophil, and heme oxygenase-1 (HO-1), an oxidative stress marker, in the BALF. In the inhalation study, transient increases in total cell and neutrophil count, CINC-1,-2 and HO-1 in the BALF were observed in the high concentration groups. Neither of the studies of ZnO nanoparticles showed persistent inflammation in the rat lung, suggesting that well-dispersed ZnO nanoparticles have low toxicity.
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Usefulness of Intratracheal Instillation Studies for Estimating Nanoparticle-Induced Pulmonary Toxicity
International journal of molecular sciences, 2016Co-Authors: Yasuo Morimoto, Hiroto Izumi, Yukiko Yoshiura, Kei Fujishima, Kazuhiro Yatera, Kazuhiro YamamotoAbstract:Inhalation studies are the gold standard for the estimation of the harmful effects of respirable chemical substances, while there is limited evidence of the harmful effects of chemical substances by Intratracheal instillation. We reviewed the effectiveness of Intratracheal instillation studies for estimating the hazards of nanoparticles, mainly using papers in which both inhalation and Intratracheal instillation studies were performed using the same nanoparticles. Compared to inhalation studies, there is a tendency in Intratracheal instillation studies that pulmonary inflammation lasted longer in the lungs. A difference in pulmonary inflammation between high and low toxicity nanoparticles was observed in the Intratracheal instillation studies, as in the inhalation studies. Among the endpoints of pulmonary toxicity, the kinetics of neutrophil counts, percentage of neutrophils, and chemokines for neutrophils and macrophages, heme oxygenase-1 (HO-1) in bronchoalveolar lavage fluid (BALF), reflected pulmonary inflammation, suggesting that these markers may be considered the predictive markers of pulmonary toxicity in both types of study. When comparing pulmonary inflammation between Intratracheal instillation and inhalation studies under the same initial lung burden, there is a tendency that the inflammatory response following the Intratracheal instillation of nanoparticles is greater than or equal to that following the inhalation of nanoparticles. If the difference in clearance in both studies is not large, the estimations of pulmonary toxicity are close. We suggest that Intratracheal instillation studies can be useful for ranking the hazard of nanoparticles through pulmonary inflammation.