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Two types of electric heating actuators used of SiCCVD fiber reinforced aluminum composite were successfully developed, which could be used at elevated temperature. The experimental results reveal that the temperature of the actuators increases with the increase of the given electric power. The maximum temperature was found to be higher the 150 and 200°C for 1-side electric heating actuator and 2-side electric heating actuator, respectively, when the electric power of about 10 W were given. It is found that the electric resistance of the actuators decreases obviously with the increase of temperature. A critical temperature was found to exist for the change of the displacement and curvature. The displacement and curvature almost remained unchanged when the temperature of the actuators was lower than the critical temperature. After that, the displacement and curvature increase with the rise of the actuator temperature. Because the 1-side and 2-side actuators have different response characteristics of the displacement and generated force, it is expected that the two types of actuators may be used in different areas. [ABSTRACT FROM AUTHOR]

The carcinogenic potential of MWCNTs is not well defined. Currently, IARC has classified MWCNT-7 as a Group 2 B material, possibly carcinogenic to humans, and all other MWCNTs as Group 3 materials, inadequate evidence in experimental animals for their carcinogenicity and not classifiable as to their carcinogenicity to humans. In this review we discuss studies that investigated the lung toxicity of well characterized MWCNTs in mice and rats. Intraperitoneal and intrascrotal injection studies identified rigid MWCNTs as hazardous materials. The assessment of lung toxicity of MWCNTs in short and medium term instillation and inhalation studies were not conclusive; therefore, these studies do not confirm the hazard of MWCNTs. However, two-year carcinogenicity studies indicate that MWCNT-7 and other MWCNTs, both thick rigid MWCNTs and thin flexible MWCNTs, are carcinogenic in test animals. Therefore, the carcinogenicity of MWCNTs in experimental animals should be reassessed. [ABSTRACT FROM AUTHOR]

Polyacrylic acid (PAA) with different concentrations of cross-linker was instilled into the trachea of rats to examine the effect of PAA crosslink density on lung disorders. Methods: F344 rats were intratracheally exposed to low and high doses of PAA with cross-linker concentrations of 0.1, 1.0, and 5.0% (CL0.1%, CL1.0%, and CL5.0%, respectively). Rats were sacrificed at 3 days, 1 week, 1 month, 3 months, and 6 months after exposure. PAA with different cross-linker concentrations caused an increase in neutrophil influx, cytokine-induced neutrophils, and chemotactic factor (CINC) in bronchoalveolar lavage fluid (BALF) from 3 days to 1 week after instillation. Lactate dehydrogenase (LDH) activity in BALF and heme oxygenase-1 (HO-1) release in lung tissue were higher in the CL0.1% exposure group during the acute phase. Lung histopathological findings also showed that severe fibrotic changes induced by CL0.1% were greater than those observed in CL1.0% and CL5.0% exposure during the observation period. CL0.1% was associated with more severe lung fibrosis, and a decrease in lung fibrosis was observed with increasing cross-linker concentrations, suggesting that the cross-link density of PAA is a physicochemical feature that affects lung disorders. [ABSTRACT FROM AUTHOR]

Objective: In our previous study, we reported that the micron-sized nickel oxide nanoparticle agglomerates induced neutrophil infiltration and the gene expression of the cytokine-induced neutrophil chemoattractant (CINC)-2αβ in a rat lung. In this study, we examined the expression of the CINCs family in the lung using the same rat model exposed to micron-sized nickel oxide nanoparticle agglomerates., Methods: The count median diameter of nickel oxide nanoparticle agglomerates suspended in saline was 1.34 μm (primary diameter: 8.41 nm). Male Wistar rats received an intratracheal instillation of 1 mg (3.3 mg/kg) of nickel oxide nanoparticles and were dissected at 3 days, 1 week, 1 month, 3 months, and 6 months after the instillation. The negative control group received an instillation of saline. The concentration of CINC-1 in the lung and the bronchoalveolar lavage fluid (BALF), CINC-2αβ in the BALF, and CINC-3 in the lung and the BALF was examined., Results: The concentration of CINC-1 was elevated at 3 days, 3 months, and 6 months in the lung tissue and from 3 days to 6 months in the BALF. The concentration of CINC-2αβ was elevated from 3 days to 3 months in the BALF. The concentration of CINC-3 was also elevated at 3 days, 1 week, 3 months, and 6 months in the lung tissue. Infiltration of neutrophil and alveolar macrophage was observed mainly in the alveoli during the observed time period., Conclusion: These results suggest that CINC-1 to -3 were totally involved in the lung injury caused by micron-sized nickel oxide nanoparticle agglomerates., (© The Author(s) 2012.)

Purpose: SN-38, a metabolite of irinotecan hydrochloride (CPT-11), is considered to play a key role in the development of diarrhea as well as in the antitumor activity of CPT-11. We have previously found that the inhibition of beta-glucuronidase, which hydrolyzes detoxified SN-38 (SN-38 glucuronide) to reform SN-38, in the lumen by eliminating the intestinal microflora with antibiotics, markedly ameliorates the intestinal toxicity of CPT-11 in rats. In this study we compared the disposition of CPT-11 and its metabolites in rats treated with and without antibiotics.Methods: Rats were given drinking water containing 1 mg/ml penicillin and 2 mg/ml streptomycin from 5 days before the administration of CPT-11 (60 mg/kg i.v.) and throughout the experiment. CPT-11, SN-38 glucuronide and SN-38 concentrations in the blood, intestinal tissues and intestinal luminal contents were determined by HPLC.Results: Antibiotics had little or no effect on the pharmacokinetics of CPT-11, SN-38 glucuronide or SN-38 in the blood, or in the tissues or contents of the small intestine, which has less beta-glucuronidase activity in its luminal contents. In contrast, antibiotics markedly reduced the AUC1-24 h of SN-38 (by about 85%) in the large intestine tissue without changing that of CPT-11, and this was accompanied by a complete inhibition of the deconjugation of SN-38 glucuronide in the luminal contents.Conclusions: These results suggest that SN-38, which results from the hydrolysis of SN-38 glucuronide by beta-glucuronidase in the intestinal microflora, contributes considerably to the distribution of SN-38 in the large intestine tissue, and that inhibition of the beta-glucuronidase activity by antibiotics results in decreased accumulation of SN-38 in the large intestine. [ABSTRACT FROM AUTHOR]

Single-wall carbon nanotubes (SWCNTs) were well-dispersed by ultrasonication to conduct an inhalation study. SWCNTs were generated using a pressurised nebuliser with liquid suspension of SWCNTs. Wistar rats were exposed to the well-dispersed SWCNT (diameter of bundle: 0.2 μm; length of bundle: 0.7 μm) for 4 weeks. The low and high mass concentrations of SWCNTs were 0.03 ± 0.003 and 0.13 ± 0.03 mg/m(3), respectively. The rats were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. There were no increases of total cell or neutrophil counts in the bronchoalveolar lavage fluid (BALF), or the concentration of cytokine-induced neutrophil chemoattractant in the lungs or BALF in both the high and low concentration-exposed groups. Pulmonary infiltration of neutrophils was not observed in either exposed group throughout the observation period. Well-dispersed SWCNT did not induce neutrophil inflammation in the lung under the conditions in the present study.

Multi-walled carbon nanotubes (MWCNTs), dispersed in suspensions consisting mainly of individual tubes, were used for intratracheal instillation and inhalation studies. Rats intratracheally received a dose of 0.2 mg, or 1 mg of MWCNTs and were sacrificed from 3 days to 6 months. MWCNTs induced a pulmonary inflammation, as evidenced by a transient neutrophil response in the low-dose groups, and presence of small granulomatous lesion and persistent neutrophil infiltration in the high-dose groups. In the inhalation study, rats were exposed to 0.37 mg/m(3) aerosols of well-dispersed MWCNTs (>70% of MWCNTs were individual fibers) for 4 weeks, and were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. The inhalation exposures delivered less amounts of MWCNTs into the lungs, and therefore less pulmonary inflammation responses was observed, as compared to intratracheal instillation. The results of our study show that well-dispersed MWCNT can produce pulmonary lesions, including inflammation.

It is important to conduct a risk assessment that includes hazard assessment and exposure assessment for the safe production and handling of newly developed nanomaterials. We conducted an inhalation study of a multi-wall carbon nanotube (MWCNT) as a hazard assessment. Male Wistar rats were exposed to well-dispersed MWCNT for 4 weeks by whole body inhalation. The exposure concentration in the chamber was 0.37 ± 0.18 mg/m³. About 70% of the MWCNTs in the chamber were single fiber. The geometric mean diameter (geometric standard deviation, GSD) and geometric mean length (GSD) of the aerosolized MWCNTs in the chamber were 63 nm (1.5) and 1.1 μm (2.7), respectively. The amounts of MWCNT deposited in the rat lungs were determined by the X-ray diffraction method and elemental carbon analysis. The average deposited amounts at 3 days after the inhalation were 68 μg/lung by the X-ray diffraction method and 76 μg/lung by elemental carbon analysis. The calculated deposition fractions were 18% and 20% in each analysis. The amount of retained MWCNT in the lungs until 3 months after the inhalation decreased exponentially and the calculated biological half times of MWCNT were 51 days and 54 days, respectively. The clearance was not delayed, but a slight increase in lung weight at 3 days after the inhalation was observed.

We described a case of ventricular fibrillation in patients with Brugada type electrocardiogram (ECG) during surgery. A 63-year-old man underwent lung lobectomy under combined general and epidural anesthesia. His preoperative ECG showed Brugada type, but he was asymptomatic and did not have a family history of sudden death. Anesthesia was induced using propofol, vecuronium and fentanyl, and maintained using propofol and lidocaine via epidural catheter. One hour into operation, ventricular fibrillation developed. After cardiac compression in a few seconds, sinus rhythm was restored and blood pressure was elevated. When the wound was sutured, ventricular fibrillation occurred again. Defibrillation was attempted immediately and sinus rhythm was restored. We diagnosed coronary spastic angina after acetylcholine challenge test. Previous report describes that the incidence of vasospasm in Brugada type ECG cases is relatively higher than those with the normal ECG. In addition, ventricular fibrillation might be induced by local anesthetics because these agents were administrated 10 minutes before the few events and balance of autonomic nervous system was changed. We conclude that strict monitoring and immediate treatment for ventricular fibrillation are important for anesthetic management in asymptomatic patient with Brugada type ECG.

We evaluated the pulmonary pathological features of rats that received a single intratracheal instillation and a 4-week inhalation of a fullerene. We used fullerene C(60) (nanom purple; Frontier Carbon Co. Ltd, Japan) in this study. Male Wistar rats received intratracheal dose of 0.1, 0.2, or 1 mg of C(60), and were sacrificed at 3 days, 1 week, 1 month, 3 months, 6 months, and 12 months. In the inhalation study, Wistar rats received C(60) or nickel oxide by whole-body inhalation for 6 h/day, 5 days/week, 4 weeks, and were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. During the observation period, no tumors or granulomas were observed in either study. Histopathological evaluation by the point counting method (PCM) showed that a high dose of C(60) (1 mg) instillation led to a significant increase of areas of inflammation in the early phase (until 1 week). In the inhalation study of the C(60)-exposed group, PCM evaluation showed significant changes in the C(60)-exposed group only at 3 days after exposure; after 1 month, no significant changes were observed. The present study demonstrated that the pulmonary inflammation pattern after exposure to well-characterized C(60) via both intratracheal and inhalation instillation was slight and transient. These results support our previous studies that showed C(60) has no significant adverse effects in intratracheal and inhalation instillation studies.

Objective: We examined the pulmonary toxicity of nickel oxide nanoparticle agglomerates in the rat lung following an intratracheal instillation., Methods: The weighted average surface primary diameter of nickel oxide nanoparticles was 8.41 nm, and the count median diameter of nickel oxide nanoparticle agglomerates suspended in saline was 1.34 µm. Male Wistar rats were exposed to 1 mg (3.3 mg/kg) of nickel oxide nanoparticles intratracheally. The control group received intratracheal instillation of saline. Rats were dissected 3 days, 1 wk, 1 mo, 3 mo, and 6 mo after the instillation. Cytokine-induced neutrophil chemoattractant (CINC)-2αβ in the lung tissue was determined by quantitative measurement of protein by ELISA., Results: The total cell count in bronchoalveolar lavage fluid (BALF) was increased persistently from 3 days to 6 mo. The neutrophil counts in BALF were also increased at 3 days, 1 wk, 3 mo, and 6 mo. In the lung tissue, infiltration of mainly neutrophils and alveolar macrophages was observed in alveoli from 3 days to 6 mo. The CINC-2αβ concentration was elevated from 3 days to 6 mo in the lung tissue., Conclusions: These results showed that micron-sized nickel oxide nanoparticle agglomerates also induced a persistent inflammatory response.

Objectives: Oxidative stress is thought to be the pathogenesis of pulmonary fibrosis induced by asbestos, and heme oxygenase-1 (HO-1) protects lung tissue against oxidative stress. We hypothesized that HO-1 is also associated with oxidative lung injury caused by exposure to potassium octatitanate whiskers (PT1), which is one of the asbestos substitutes., Methods: Male Wistar rats were administered 1 mg or 2 mg PT1 suspended in saline by a single intratracheal instillation and were sacrificed after recovery for 3 days, 1 wk, 1 mo, 3 mo or 6 mo. Gene expression of HO-1 protein and mRNA and immunostaining were investigated in rat lungs., Results: HO-1 protein expression was increased from 3 days to 1 mo and at 6 mo in the 1 or 2 mg PT1-exposed groups, and the gene expression of HO-1 mRNA was also increased at 3 days and from 1 mo to 6 mo. HO-1-positive cells were mainly found in the alveolar macrophages and the bronchial epithelial cells in immunostaining., Conclusions: These findings suggest that HO-1 is involved in lung damage caused by PT1.

In order to investigate whether or not dispersed nanoparticles have an effect of inflammation and fibrosis on animals, we developed a nanoparticle generation system and examined the gene expression of matrix metalloproteinase (MMP) and tissue inhibitor matrix proteinase (TIMP) in rat lung containing inhaled nickel oxide (NiO) or titanium dioxide (TiO(2)) nanoparticles. In both experiments, Wistar male rats were exposed to NiO or TiO(2) nanoparticles for 4 wk (6 h/day). The geometric mean diameters of NiO and TiO(2) in the chamber were 139 ± 12 nm and 51 ± 9 nm, respectively. The average concentration of the particle number of NiO and TiO(2) was 1.0E+05 /cm(3) and 2.8E+05 /cm(3), respectively. At 4 d, 1 and 3 months after the end of the inhalation, the rats exposed to these particles were sacrificed and the gene expressions of MMP-2, TIMP-2 and type I collagen were measured using RT-PCR. Pathological finding revealed that there was minimum inflammation with nickel oxide only at 4 d and no change with titanium oxide. However, there were no changes of the gene expression of MMP-2, TIMP-2, and type I collagen in either the NiO or TiO(2) exposure groups. In this study, inhalation of nickel oxide and titanium dioxide nanoparticles did not induce the gene expression of MMP-2 and TIMP-2 mRNA in rat lungs.

The objective of this study was to examine what kinds of cytokines are related to lung disorder by well-dispersed nanoparticles. The mass median diameter of nickel oxide in distilled water was 26 nm. Rats intratracheally received 0.2 mg of nickel oxide suspended in distilled water, and were sacrificed from three days to six months. The concentrations of 21 cytokines including inflammation, fibrosis and allergy-related ones were measured in the lung. Infiltration of alveolar macrophages was observed persistently in the nickel oxide-exposed group. Expression of macrophage inflammatory protein-1alpha showed a continued increase in lung tissue and broncho-alveolar lavage fluid (BALF) while interleukin-1alpha (IL-1alpha), IL-1beta in lung tissue and monocyte chemotactic protein-1 in BALF showed transient increases. Taken together, it was suggested that nano-agglomerates of nickel oxide nanoparticles have a persistent inflammatory effect, and the transient increase in cytokine expression and persistent increases in CC chemokine were involved in the persistent pulmonary inflammation.

Background: We used fullerenes, whose dispersion at the nano-level was stabilized by grinding in nitrogen gas in an agitation mill, to conduct an intratracheal instillation study and an inhalation exposure study. Fullerenes were individually dispersed in distilled water including 0.1% Tween 80, and the diameter of the fullerenes was 33 nm. These suspensions were directly injected as a solution in the intratracheal instillation study. The reference material was nickel oxide in distilled water. Wistar male rats intratracheally received a dose of 0.1 mg, 0.2 mg, or 1 mg of fullerenes and were sacrificed after 3 days, 1 week, 1 month, 3 months, and 6 months. In the inhalation study, Wistar rats were exposed to fullerene agglomerates (diameter: 96 +/- 5 nm; 0.12 +/- 0.03 mg/m3; 6 hours/days for 5 days/week) for 4 weeks and were sacrificed at 3 days, 1 month, and 3 months after the end of exposure. The inflammatory responses and gene expression of cytokine-induced neutrophil chemoattractants (CINCs) were examined in rat lungs in both studies., Results: In the intratracheal instillation study, both the 0.1 mg and 0.2 mg fullerene groups did not show a significant increase of the total cell and neutrophil count in BALF or in the expression of CINC-1,-2alphabeta and-3 in the lung, while the high-dose, 1 mg group only showed a transient significant increase of neutrophils and expression of CINC-1,-2alphabeta and -3. In the inhalation study, there were no increases of total cell and neutrophil count in BALF, CINC-1,-2alphabeta and-3 in the fullerene group., Conclusion: These data in intratracheal instillation and inhalation studies suggested that well-dispersed fullerenes do not have strong potential of neutrophil inflammation.

We experienced a case of submucosal hematoma of the esophagus noticed after cervical anterior spinal fusion (ASF) between C7 and T1 for ossification of posterior longitudinal ligament (OPLL). The patient was a 68-year-old man, and no abnormality was found in the preoperative examinations. Anesthesia was induced and maintained with remifentanil, propofol and vecuronium. Tracheal intubation was performed using fiberscope uneventfully, and gastric tube and esophageal stethoscope were inserted into the esophagus smoothly. The operation was completed in 7 hours and 10 minutes. When we removed the gastric tube and the esophageal stethoscope after the operation, no bloody secretion was noticed. The next day, the patient complained of melena, and gastrointestinal endoscopy showed a submucosal hematoma extending from the posterior wall of the cervico-thoracic border in the esophagus to the cardia. Submucosal hematoma of the esophagus is a rare complication. In this case, surgical procedure was suspected to have caused the hematoma, since the upper end of the hematoma corresponded to the surgical field.

Since nanoparticles easily agglomerate to form larger particles, it is important to maintain the size of their agglomerates at the nano-level to evaluate the harmful effect of the nanoparticles. We prevented agglomeration of nickel oxide nanoparticles by ultrasound diffusion and filtration, established an acute exposure model using animals, and examined inflammation and chemokine expression. The mass median diameter of nickel oxide nanoparticle agglomerates suspended in distilled water for intratracheal instillation was 26 nm (8.41 nm weighted average surface primary diameter). Male Wistar rats received intratracheal instillation of nickel oxide nanoparticles at 0.1 mg (0.33 mg/kg) or 0.2 mg (0.66 mg/kg), and were dissected 3 days, 1 week, 1 month, 3 months, and 6 months after the instillation. The control group received intratracheal instillation of distilled water. Three chemokines (cytokine-induced neutrophil chemoattractant-1 (CINC-1), CINC-2alphabeta, and CINC-3) in the lung tissue and bronchoalveolar lavage fluid (BALF) were determined by quantitative measurement of protein by ELISA. Both CINC-1 and CINC-2alphabeta concentration was elevated from day 3 to 3 months in lung tissue and from day 3 to 6 months in BALF. On the other hand, CINC-3 was elevated on day 3 in both lung tissue and BALF, and then decreased. The total cell and neutrophil counts in BALF were increased from day 3 to 3 months. In lung tissue, infiltration of mainly neutrophils and alveolar macrophages was observed from day 3 to 6 months in alveoli. These results suggest that CINC was involved in lung injury by nickel oxide nanoparticles.

In order to evaluate the chronic effect of polymerized toner particles on the lung, inflammation- and fibrosis-related genes were analyzed and 8-hydroxydeoxyguanosine (8-OHdG) was examined by using the lung tissue of rats subjected to 24 months of toner inhalation exposure. Wistar female rats were divided into four groups (5 weeks old, 30 rats in each): the high concentration exposure group (16.3 +/- 0.6 mg/m(3)), the medium concentration exposure group (4.4 +/- 0.3 mg/m(3)), the low concentration exposure group (1.6 +/- 0.2 mg/m(3)), and the control group (clean air). The material used was black toner, and its aerodynamic diameter in the exposure chamber was 3.0 microm. The rats were exposed to the material for 24 months (6 hours/day, 5 days/week) and dissected after the exposure period. RNA was extracted from one lung and the gene expression related to inflammation and fibrosis. Matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2), and type I collagen were analyzed according to the ratio of each gene/beta-actin. Also, 8-OHdG level in the lung tissue was measured by HPLC with an electrochemical detector. Small fibrotic foci were found in the toner exposed groups; however, progressive or irreversible fibrosis was not found. The incidence of small fibrotic foci and cell aggregation increased in a dose-dependent manner. There were no significant differences of expression of MMP-2, TIMP-2, and type I collagen between the control group and each exposed group. Lung tumors did not develop in each group. A significant production of 8-OHdG was not observed in the toner exposed groups. In conclusion, toner produced by polymerization was not associated with evidence of carcinogenesis in this experiment.