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1.
Nanotoxicology ; 18(2): 214-228, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38557361

RESUMO

Carbon nanotubes (CNTs) are increasingly being used in industrial applications, but their toxicological data in animals and humans are still sparse. To assess the toxicological dose-response of CNTs and to evaluate their pulmonary biopersistence, their quantification in tissues, especially lungs, is crucial. There are currently no reference methods or reference materials for low levels of CNTs in organic matter. Among existing analytical methods, few have been fully and properly validated. To remedy this, we undertook an inter-laboratory comparison on samples of freeze-dried pig lung, ground and doped with CNTs. Eight laboratories were enrolled to analyze 3 types of CNTs at 2 concentration levels each in this organic matrix. Associated with the different analysis techniques used (specific to each laboratory), sample preparation may or may not have involved prior digestion of the matrix, depending on the analysis technique and the material being analyzed. Overall, even challenging, laboratories' ability to quantify CNT levels in organic matter is demonstrated. However, CNT quantification is often overestimated. Trueness analysis identified effective methods, but systematic errors persisted for some. Choosing the assigned value proved complex. Indirect analysis methods, despite added steps, outperform direct methods. The study emphasizes the need for reference materials, enhanced precision, and organized comparisons.


Assuntos
Pulmão , Nanotubos de Carbono , Nanotubos de Carbono/química , Nanotubos de Carbono/toxicidade , Animais , Suínos , Pulmão/química , Pulmão/efeitos dos fármacos , Laboratórios/normas , Compostos Orgânicos/análise , Compostos Orgânicos/química
2.
Sensors (Basel) ; 23(17)2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37687934

RESUMO

Recently, the application of cobalt iron boron (CoFeB) thin films in magnetic sensors has been widely studied owing to their high magnetic moment, anisotropy, and stability. However, most of these studies were conducted on rigid silicon substrates. For diverse applications of magnetic and angle sensors, it is important to explore the properties of ferromagnetic thin films grown on nonrigid deformable substrates. In this study, representative deformable substrates (polyimide (PI), polyethylene naphthalate (PEN), and polydimethylsiloxane (PDMS)), which can be bent or stretched, were used to assess the in-plane magnetic field angle-dependent properties of amorphous Ta/CoFeB/MgO/Ta thin films grown on deformable substrates. The effects of substrate roughness, tensile stress, deformable substrate characteristics, and sputtering on magnetic properties, such as the coercive field (Hc), remanence over saturation magnetization (Mr/Ms), and biaxial characteristics, were investigated. This study presents an unconventional foundation for exploring deformable magnetic sensors capable of detecting magnetic field angles.

3.
Microfluid Nanofluidics ; 27(11): 1-10, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38196842

RESUMO

Early detection of pulmonary responses to silica aerosol exposure, such as lung inflammation as well as early identification of silicosis initiation, is of great importance in disease prevention of workers. In this study, to early screen the health condition of the workers who are exposed to respirable silica dusts, an immunoassay lab on a chip (LOC) was designed, developed and fully characterized for analyzing Clara cell protein 16 (CC16) in serum which has been considered as one of the potential biomarkers of lung inflammation or lung damage due to the respirable silica dusts. Sandwich immunoassay of CC16 was performed on the LOC developed with a custom-designed portable analyzer using artificial serums spiked with CC16 protein first and then human serums obtained from the coal mine workers exposed to the respirable silica-containing dusts. The dynamic range of CC16 assay performed on the LOC was in a range of 0.625-20 ng/mL, and the achieved limit of detection (LOD) was around 0.35 ng/mL. The assay results of CC16 achieved from both the developed LOC and the conventional 96 well plate showed a reasonable corelation. The correlation between the conventional reader and the developed portable analyzer was found to be reasonable, resulting in R2 ~ 0.93. This study shows that the LOC developed for the early detection of CC16 can be potentially applied for the development of a field-deployable point-of-care testing (POCT) for the early monitoring of the field workers who are exposed to silica aerosol.

4.
J Knee Surg ; 32(3): 274-279, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29618147

RESUMO

The purpose of this study was to investigate whether the location of the hinge affects the incidence of hinge fracture during medial closing-wedge distal femoral varus osteotomy (DFVO). Twenty knees from 10 fresh-frozen human cadavers (mean age, 75 ± 17 years) were used to perform uniplanar medial closing-wedge DFVO with a 7-mm wedge. Each specimen was randomly assigned to either group A (supracondylar hinge) or group B (lateral condylar hinge). The incidence of hinge fracture and stability was compared between both groups after uniplanar medial closing-wedge DFVO. In group A, 8 of 10 knees had a lateral cortex fracture during closure of the osteotomy gap, and all fractured knees were unstable. Two knees with an intact lateral cortical hinge showed stability under manual valgus and varus forces. After intentional breakage of the lateral cortical hinge, both knees were found to be unstable under the same force. In group B, 2 of 10 knees had a lateral cortex fracture, and 8 knees had no fractures. All specimens were found to be stable under manual valgus and varus forces. After intentional breakage of the lateral cortical hinge in group B, 2 knees were unstable, while 8 knees remained stable. This study showed a significantly higher incidence of lateral cortical hinge fracture and instability in group A than in group B during closure of the osteotomy gap.


Assuntos
Fraturas do Fêmur/prevenção & controle , Fêmur/cirurgia , Articulação do Joelho/fisiopatologia , Articulação do Joelho/cirurgia , Osteotomia/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Cadáver , Feminino , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Próteses e Implantes , Tíbia/cirurgia
5.
Nanotoxicology ; 12(3): 224-238, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29385887

RESUMO

Graphene oxides possess unique physicochemical properties with important potential applications in electronics, pharmaceuticals, and medicine. However, the toxicity following inhalation exposure to graphene oxide has not yet been clarified. Therefore, this study conducted a short-term graphene oxide inhalation toxicity analysis using a nose-only inhalation exposure system and male Sprague-Dawley rats. A total of four groups (15 rats per group) were exposed: (1) control (fresh air), (2) low concentration (0.76 ± 0.16 mg/m3), (3) moderate concentration (2.60 ± 0.19 mg/m3), and (4) high concentration (9.78 ± 0.29 mg/m3). The rats were exposed to graphene oxide for 6 h/day for 5 days, followed by recovery for 1, 3, and 21 days. No significant body or organ weight changes were noted after the short-term exposure or during the recovery period. Similarly, no significant systemic effects of toxicological importance were noted in the hematological assays, bronchoalveolar lavage fluid (BAL) inflammatory markers, BAL fluid cytokines, or blood biochemical assays following the graphene oxide exposure or during the post-exposure observation period. Moreover, no significant differences were observed in the BAL cell differentials, such as lymphocytes, macrophages, or polymorphonuclear cells. Graphene oxide-ingested alveolar macrophages as a spontaneous clearance reaction were observed in the lungs of all the concentration groups from post 1 day to post 21 days. Histopathological examination of the liver and kidneys did not reveal any significant test-article-relevant histopathological lesions. Importantly, similar to previously reported graphene inhalation data, this short-term nose-only inhalation study found only minimal or unnoticeable graphene oxide toxicity in the lungs and other organs.


Assuntos
Grafite/administração & dosagem , Grafite/toxicidade , Nanoestruturas/administração & dosagem , Nanoestruturas/toxicidade , Óxidos/administração & dosagem , Óxidos/toxicidade , Administração por Inalação , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Líquido da Lavagem Broncoalveolar/citologia , Citocinas/metabolismo , Exposição por Inalação , Rim/efeitos dos fármacos , Contagem de Leucócitos , Fígado/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
6.
Knee Surg Relat Res ; 30(1): 3-16, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29298461

RESUMO

PURPOSE: The purpose of this review is to compare the clinical and radiological outcomes between open and closed wedge distal femoral varus osteotomy (DFO). METHODS: A literature search of online databases (MEDLINE, EMBASE, and Cochrane Library database) was made in addition to manual search of major orthopedic journals. Data were searched from the time period of January 1990 to October 2016. A modified Coleman Methodology Score system was used to assess the methodologic quality of the included studies. A total of 20 studies were included in the review. All studies were level IV evidence. RESULTS: Comparative analysis of open and closed wedge DFO did not demonstrate clinical and radiological differences. The survival rates were also similar. Five studies (56%) on open wedge DFO mentioned the need for either bone grafting or substitute for osteotomy gap filling and reported higher incidences of reoperation for plate removal than the closed wedge DFO studies. CONCLUSIONS: The present systematic review showed similar performance between open and closed wedge DFO. Outcomes including survival rates were not statistically significantly different. However, additional bone grafting or substitutes were often needed to prevent delayed union or nonunion for open wedge techniques. Additional operations for plate removal were commonly required due to plate irritation in both techniques.

7.
Int J Pharm ; 528(1-2): 692-704, 2017 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-28642202

RESUMO

Heterogeneity of cancer cells and drug resistance require multiple therapeutic approaches for comprehensive treatment. In this study, temperature-sensitive liposomes containing anti-cancer agent tanespimycin (17-AAG) and photosensitizer IR 820 were developed for combination of phototherapy and chemotherapy. The temperature-sensitive liposomes composed of DPPC, cholesterol, DSPE-PEG, 17-AAG, and IR 820 (LP-AI) at weight ratio of 35/15/3/2/2 were formulated as a thin film using extrusion and evaluated for particle size, morphology and drug release profile. Furthermore, the anticancer effect of combined therapy was examined in vitro and in vivo in SCC-7 and MCF-7 cell lines. As a result, LP-AI was prepared at particle size of 166.7±1.3nm, PDI of 0.153±0.012, and ζ-potential of -32.6±0.8mV. After NIR irradiation (660 and 808nm laser), LP-AI could generate heat and ROS and enhance drug release from nanoparticles which were useful to kill the cancer cells. These were confirmed by in vitro cytotoxicity as well as in vivo effective ablation of tumors. In conclusion, fast drug release and enhanced treatment efficacy of LP-AI indicate the potential of integrating photo- and chemotherapy for synergistic anti-cancer effects.


Assuntos
Antineoplásicos/farmacologia , Benzoquinonas/farmacologia , Lactamas Macrocíclicas/farmacologia , Lipossomos/química , Fotoquimioterapia , Temperatura , Linhagem Celular Tumoral , Humanos
8.
Yonsei Med J ; 58(4): 878-883, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28541005

RESUMO

PURPOSE: Recurrent patellar dislocation is often associated with genu valgum. The purpose of this study was to analyze the short-term results of single-incision, closing-wedge distal femoral osteotomy (CWDFO) combined with medial reefing and lateral release for recurrent patellar instability with genu valgum. MATERIALS AND METHODS: Combined CWDFO/medial reefing/lateral release was performed on 10 knees. Clinical evaluation was based on pre- and postoperative Knee Society Score (KSS) and Kujala patellofemoral score. Radiographic evaluation was performed with reference to the weight-bearing line (WBL), the femorotibial angle (FTA), and the mechanical lateral distal femoral angles in the knee-standing view. RESULTS: At a mean follow-up of 20±11.7 months (range, 12-42 months), KSS scores improved significantly, from 46.7±5.2 preoperatively to 87±4.4 postoperatively (p<0.001), as did the Kujala score, from 44±8 preoperatively to 86.6±6.8 postoperatively (p<0.001). The WBL decreased significantly, from 76±7% preoperatively to 41±11% postoperatively (p<0.001). The FTA was improved significantly, from 12.7±1.7° preoperatively to 4±4° postoperatively (p<0.001), as was the mLDFA, from 83±4° preoperatively to 91±1.3° postoperatively (p<0.001). CONCLUSION: Use of single-incision CWDFO combined with medial reefing and lateral release prevents patellar dislocation, corrects deformity, and improves clinical outcomes.


Assuntos
Fêmur/cirurgia , Geno Valgo/complicações , Geno Valgo/cirurgia , Osteotomia/métodos , Luxação Patelar/complicações , Luxação Patelar/cirurgia , Adulto , Demografia , Feminino , Fêmur/diagnóstico por imagem , Fêmur/patologia , Seguimentos , Geno Valgo/diagnóstico por imagem , Humanos , Masculino , Luxação Patelar/diagnóstico por imagem , Cuidados Pré-Operatórios , Resultado do Tratamento , Adulto Jovem
9.
Colloids Surf B Biointerfaces ; 155: 83-92, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28410515

RESUMO

When exposed to cancer cells, cytotoxic drugs such as doxorubicin (DOX) can lead to the induction of heat shock protein 90 (Hsp90), a molecular chaperone associated with a number of cancer-related client proteins, and result in cell survival. Co-administration of DOX with tanespimycin (TNP), an Hsp90 inhibitor, can sensitize the cancer cells to the cytotoxic effects of DOX. The effect of such a combination has been found to depend on the schedule of administration. Sequential administration of DOX and TNP has been linked to highly synergistic combination effects. Therefore, we aimed to develop folate-receptor targeted hybrid lipid-core nanocapsules comprising a hybrid lipid core lodging TNP and a polymeric corona lodging DOX (F-DTN). These nanocarriers were capable of delivering DOX and TNP sequentially, which was well demonstrated by an in vitro release study. The in vitro release profiles displayed pH-dependent and sustained release features. F-DTN exhibited excellent morphological characteristics with highly monodispersed particles. In vitro tests with F-DTN in MCF-7 cell line demonstrated exceptional cytotoxicity, with high cellular uptake and apoptosis. These findings were appreciably more assertive than tests with free individual drugs (DOX, TNP), free drug combination (DOX/TNP), or non-folate receptor-targeted hybrid lipid-core nanocapsules (DTN). In vivo pharmacokinetic study revealed noticeable enhancement of bioavailability and plasma circulation time of the drugs when encapsulated in the carrier system. Therefore, hybrid lipid-core nanocapsules have the potential to be utilized for application in folate receptor-targeted combination chemotherapy.


Assuntos
Antineoplásicos/farmacologia , Benzoquinonas/farmacologia , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Receptor 1 de Folato/metabolismo , Lactamas Macrocíclicas/farmacologia , Nanocápsulas/química , Proteínas de Neoplasias/metabolismo , Células A549 , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Benzoquinonas/química , Benzoquinonas/farmacocinética , Biomarcadores/metabolismo , Dimetil Sulfóxido/química , Doxorrubicina/química , Doxorrubicina/farmacocinética , Ácidos Graxos Monoinsaturados/química , Receptor 1 de Folato/genética , Ácido Fólico/química , Ácido Fólico/metabolismo , Expressão Gênica , Humanos , Injeções Intravenosas , Lactamas Macrocíclicas/química , Lactamas Macrocíclicas/farmacocinética , Células MCF-7 , Masculino , Micelas , Nanocápsulas/administração & dosagem , Nanocápsulas/ultraestrutura , Proteínas de Neoplasias/genética , Fosfatidiletanolaminas/química , Compostos de Amônio Quaternário/química , Ratos , Ratos Sprague-Dawley
10.
Knee Surg Sports Traumatol Arthrosc ; 25(3): 767-772, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28220190

RESUMO

PURPOSE: The purpose of this retrospective comparative study was to evaluate and compare, radiographically and clinically, progression of osteoarthritis (OA) in the patellofemoral (PF) compartment after open-wedge high tibial osteotomy (OWHTO), and unicompartmental knee arthroplasty (UKA) over a minimum follow-up of 5 years. METHODS: In this study, 42 knees in an OWHTO group were compared with 59 knees in a UKA group in terms of radiographic parameters, such as the grading system for OA progression in the PF compartment, and clinical parameters, such as the PF pain and function scores over a minimum follow-up of 5 years. RESULTS: There was no significant difference of OA progression in the PF compartment between the two groups on knee radiography. Compared with the preoperative grades, the UKA group showed significant progression of OA in the medial PF compartment at the final follow-up, whereas the medial PF compartment showed significant stepwise progression by only one grade when compared to the OWHTO group. The PF pain and function scores showed no statistical differences between the two groups at the final follow-up, regardless of OA progression. CONCLUSIONS: There was no significant difference between OWHTO and UKA in terms of progression of OA in the PF compartment or deterioration of PF function score over a minimum follow-up of 5 years. However, the medial PF compartment of the UKA group was minimal, and worsened or progressed by only one grade. LEVEL OF EVIDENCE: III.


Assuntos
Artroplastia do Joelho/métodos , Osteoartrite do Joelho/cirurgia , Osteotomia/métodos , Articulação Patelofemoral/cirurgia , Idoso , Progressão da Doença , Feminino , Humanos , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Articulação Patelofemoral/diagnóstico por imagem , Radiografia , Estudos Retrospectivos
11.
Inhal Toxicol ; 29(12-14): 567-576, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29400116

RESUMO

Synthetic amorphous silica nanoparticles (SiNPs) are one of the most applied nanomaterials and are widely used in a broad variety of industrial and biomedical fields. However, no recent long-term inhalation studies evaluating the toxicity of SiNPs are available and results of acute studies are limited. Thus, we conducted a subacute inhalation toxicity study of SiNPs in Sprague-Dawley rats using a nose-only inhalation system. Rats were separated into four groups and target concentrations selected in this study were as follows: control (fresh air), low- (0.407 ± 0.066 mg/m3), middle- (1.439 ± 0.177 mg/m3) and high-concentration group (5.386 ± 0.729 mg/m3), respectively. The rats were exposed to SiNPs for four consecutive weeks (6 hr/day, 5 days/week) except for control group of rats which received filtered fresh air. After 28-days of inhalation exposure to SiNPs, rats were sacrificed after recovery periods of one, seven and 28 days. Although there were minimal toxic changes such as temporary decrease of body weight after exposure, increased levels of red blood cells (RBCs) and hemoglobin (Hb) concentration, the lung histopathological findings and inflammatory markers in bronchoalveolar lavage (BAL) fluid including polymorphonuclear (PMN) leukocyte, lactate dehydrogenase (LDH), albumin and protein did not show significant changes at any recovery period. The results of this study suggest that the subacute inhalation of SiNPs had no toxic effects on the lung of rats at the concentrations and selected time points used in this study.


Assuntos
Exposição por Inalação , Pulmão/efeitos dos fármacos , Nanopartículas/administração & dosagem , Dióxido de Silício/administração & dosagem , Aerossóis/administração & dosagem , Aerossóis/metabolismo , Aerossóis/toxicidade , Animais , Exposição por Inalação/efeitos adversos , Pulmão/metabolismo , Masculino , Nanopartículas/metabolismo , Nanopartículas/toxicidade , Ratos , Ratos Sprague-Dawley , Dióxido de Silício/metabolismo , Dióxido de Silício/toxicidade , Distribuição Tecidual/efeitos dos fármacos , Distribuição Tecidual/fisiologia
12.
Knee Surg Relat Res ; 28(4): 277-282, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-27894174

RESUMO

PURPOSE: This study was to determine the efficacy of iliac crest reconstruction using bone cement in reducing pain and morbidity at the donor site in patients undergoing open wedge high tibial osteotomy (OWHTO) with tricortical iliac crest autologous graft. MATERIALS AND METHODS: Thirty-three patients who underwent iliac crest reconstruction using polymethyl methacrylate (PMMA) bone cement (group A) and thirty patients who had no iliac crest reconstruction (group B) were enrolled in this study. All patients were evaluated for pain and functional disability related to graft harvesting using the pain and functional visual analogue scale (VAS) score during hospital stay and at 6 weeks, 3 months, and 6 months postoperatively. RESULTS: There was significant difference between the two groups in terms of pain and function. The pain VAS score was significantly lower in group A than group B during the first 2 weeks postoperatively (p=0.04) and the functional VAS score was also significantly lower in group A during the first 2 weeks postoperatively (p<0.001) in terms of breathing, sitting up from the supine position, and standing up with crutches from the sitting position. CONCLUSIONS: Iliac crest donor site reconstruction using PMMA bone cement in patients undergoing OWHTO significantly decreased pain and improved function during the first 2 weeks postoperatively when compared to patients who underwent OWHTO without iliac crest reconstruction.

13.
Knee Surg Sports Traumatol Arthrosc ; 24(8): 2567-77, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26423055

RESUMO

PURPOSE: Medial opening wedge high tibial osteotomy (HTO) has become increasingly popular as an alternative to lateral closing wedge osteotomy for the treatment of medial compartment knee osteoarthritis with varus deformity. The present systematic review was conducted to provide an objective analysis of total knee arthroplasty (TKA) outcomes following previous knee osteotomy (medial opening wedge vs. lateral closing wedge). METHODS: A literature search of online databases (MEDLINE, EMBASE, Cochrane Library database) was made, in addition to manual search of major orthopaedic journals. The methodological quality of each of the studies was assessed on the Newcastle-Ottawa Scale and Effective Practice and Organization of Care. A total of ten studies were included in the review. There were eight studies with Level IV and two studies with Level III evidence. RESULTS: Eight studies reported clinical and radiologic scores. Comparative studies between TKA following medial opening and lateral closing wedge HTO did not demonstrate statistically significant clinical and radiologic differences. The revision rates were similar. However, more technical issues during TKA surgery after lateral closing wedge HTO were mentioned than the medial open wedge group. The quadriceps snip, tibial tubercle osteotomy, and lateral soft tissue release were more frequently needed in the lateral closing wedge HTO group. In addition, because of loss of proximal tibia bone geometry in the lateral closing wedge HTO group, concerns such as tibia stem impingement in the lateral tibial cortex was noted. CONCLUSION: The present systematic review suggests that TKA after medial opening and lateral closing wedge HTO showed similar performance. Clinical and radiologic outcome including revision rates did not statistically differ from included studies. However, there are more surgical technical concerns in TKA conversion from lateral closing wedge HTO than from the medial opening wedge HTO group. LEVEL OF EVIDENCE: IV.


Assuntos
Artroplastia do Joelho , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Osteotomia/métodos , Tíbia/cirurgia , Humanos , Músculo Quadríceps/cirurgia , Reoperação , Resultado do Tratamento
14.
Nanotoxicology ; 10(7): 891-901, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26691980

RESUMO

Graphene, a two-dimensional engineered nanomaterial, is now being used in many applications, such as electronics, biological engineering, filtration, lightweight and strong nanocomposite materials, and energy storage. However, there is a lack of information on the potential health effects of graphene in humans based on inhalation, the primary engineered nanomaterial exposure pathway in workplaces. Thus, an inhalation toxicology study of graphene was conducted using a nose-only inhalation system for 28 days (6 h/day and 5 days/week) with male Sprague-Dawley rats that were then allowed to recover for 1-, 28-, and 90-day post-exposure period. Animals were separated into 4 groups (control, low, moderate, and high) with 15 male rats (5 rats per time point) in each group. The measured mass concentrations for the low, moderate, and high exposure groups were 0.12, 0.47, and 1.88 mg/m(3), respectively, very close to target concentrations of 0.125, 0.5, and 2 mg/m(3). Airborne graphene exposure was monitored using several real-time instrumentation over 10 nm to 20 µm for size distribution and number concentration. The total and respirable elemental carbon concentrations were also measured using filter sampling. Graphene in the air and biological media was traced using transmission electron microscopy. In addition to mortality and clinical observations, the body weights and food consumption were recorded weekly. At the end of the study, the rats were subjected to a full necropsy, blood samples were collected for blood biochemical tests, and the organ weights were measured. No dose-dependent effects were recorded for the body weights, organ weights, bronchoalveolar lavage fluid inflammatory markers, and blood biochemical parameters at 1-day post-exposure and 28-day post-exposure. The inhaled graphenes were mostly ingested by macrophages. No distinct lung pathology was observed at the 1-, 28- and 90-day post-exposure. The inhaled graphene was translocated to lung lymph nodes. The results of this 28-day graphene inhalation study suggest low toxicity and a NOAEL of no less than 1.88 mg/m(3).


Assuntos
Grafite/toxicidade , Exposição por Inalação/efeitos adversos , Pulmão/efeitos dos fármacos , Nanoestruturas/toxicidade , Animais , Biomarcadores/metabolismo , Líquido da Lavagem Broncoalveolar , Relação Dose-Resposta a Droga , Grafite/química , Humanos , Pulmão/metabolismo , Masculino , Nanoestruturas/química , Nível de Efeito Adverso não Observado , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
15.
Biomed Res Int ; 2015: 376756, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26295037

RESUMO

Graphene is receiving increased attention due to its potential widespread applications in future. However, the health effects of graphene have not yet been well studied. Therefore, this study examined the pulmonary effects of graphene oxide using male Sprague-Dawley rats and a single 6-hour nose-only inhalation technique. Following the exposure, the rats were allowed to recover for 1 day, 7 days, or 14 days. A total of three groups were compared: control (fresh air), low concentration (0.46 ± 0.06 mg/m(3)), and high concentration (3.76 ± 0.24 mg/m(3)). The exposure to graphene oxide did not induce significant changes in the body weights, organ weights, and food consumption during the 14 days of recovery time. The microalbumin and lactate dehydrogenase levels in the bronchoalveolar lavage (BAL) fluid were not significantly changed due to the exposure. Similarly, total cell count, macrophages, polymorphonuclear leukocytes, and lymphocytes were not significantly altered in the BAL fluid. Plus, the histopathological examination of the rat lungs only showed an uptake of graphene oxide in the alveolar macrophages of the high-concentration group. Therefore, these results demonstrate that the single inhalation exposure to graphene oxide induce minimal toxic responses in rat lungs at the concentrations and time points used in the present study.


Assuntos
Grafite/toxicidade , Pulmão/patologia , Nanoestruturas/toxicidade , Óxidos/toxicidade , Animais , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar , Inflamação/patologia , Exposição por Inalação , Pulmão/efeitos dos fármacos , Masculino , Nanoestruturas/ultraestrutura , Tamanho do Órgão/efeitos dos fármacos , Tamanho da Partícula , Ratos Sprague-Dawley
16.
J Korean Med Sci ; 30(2): 140-4, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25653483

RESUMO

Coal workers' pneumoconiosis (CWP) is characterized as a chronic inflammation of the lung associated with activation of macrophages and endothelial cells in the lung. The aim of the present study was to compare the levels of serum interleukin-8 (IL-8), macrophage inflammatory protein-1α (MIP-α), and intercellular adhesion molecule-1 (ICAM-1) as biomarkers for progressive massive fibrosis (PMF) in 106 subjects (27 non-CWP and 79 CWP patients). The levels of serum IL-8 (P<0.001) and ICAM-1 (P=0.001) of subjects with PMF were higher than those of non-CWP subjects. The IL-8 levels of PMF subjects were also higher than those of simple CWP subjects (P=0.003). Among the subjects without PMF, IL-8 levels in the subjects with International Labour Organization (ILO) category II or III were higher than those in the subjects with ILO category 0 (P=0.006) and with category I (P=0.026). These results suggest that high serum levels of IL-8 and ICAM-1, which are important as neutrophil attractants and adhesion molecules, are associated with PMF.


Assuntos
Antracose/sangue , Quimiocina CCL3/sangue , Molécula 1 de Adesão Intercelular/sangue , Interleucina-8/sangue , Fibrose Pulmonar/sangue , Idoso , Antracose/patologia , Biomarcadores/sangue , Minas de Carvão , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/sangue , Doenças Profissionais/patologia , Fibrose Pulmonar/patologia
17.
Nanotoxicology ; 9(8): 1023-31, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25697182

RESUMO

Graphene has recently been attracting increasing attention due to its unique electronic and chemical properties and many potential applications in such fields as semiconductors, energy storage, flexible electronics, biosensors and medical imaging. However, the toxicity of graphene in the case of human exposure has not yet been clarified. Thus, a 5-day repeated inhalation toxicity study of graphene was conducted using a nose-only inhalation system for male Sprague-Dawley rats. A total of three groups (20 rats per group) were compared: (1) control (ambient air), (2) low concentration (0.68 ± 0.14 mg/m(3) graphene) and (3) high concentration (3.86 ± 0.94 mg/m(3) graphene). The rats were exposed to graphene for 6 h/day for 5 days, followed by recovery for 1, 3, 7 or 28 days. The bioaccumulation and macrophage ingestion of the graphene were evaluated in the rat lungs. The exposure to graphene did not change the body weights or organ weights of the rats after the 5-day exposure and during the recovery period. No statistically significant difference was observed in the levels of lactate dehydrogenase, protein and albumin between the exposed and control groups. However, graphene ingestion by alveolar macrophages was observed in the exposed groups. Therefore, these results suggest that the 5-day repeated exposure to graphene only had a minimal toxic effect at the concentrations and time points used in this study.


Assuntos
Grafite/administração & dosagem , Grafite/toxicidade , Macrófagos Alveolares/metabolismo , Administração por Inalação , Albuminas/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Grafite/farmacocinética , L-Lactato Desidrogenase/metabolismo , Macrófagos Alveolares/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Proteínas/metabolismo , Ratos , Fatores de Tempo
18.
Nanotoxicology ; 9(6): 802-11, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25395166

RESUMO

While many in vivo and in vitro toxicology studies of multi-walled carbon nanotubes (MWCNTs) have already indicated that exposure to MWCNTs can potentially induce health effects in humans, the actual health effects of MWCNTs among exposed workers are not yet known. Moreover, the levels of exposure and internal doses of MWCNTs are becoming more and more important for estimating the health effects resulting from exposure to MWCNTs. However, information on biomonitoring and exposure to MWCNTs remains limited. Therefore, the authors conducted a health surveillance study in a workplace that manufactures MWCNTs, including assessment of the personal and area exposure levels to MWCNTs, a walk-through evaluation of the manufacturing process, and collection of blood and exhaled breath condensates (EBCs) from the MWCNT manufacturing and office workers. In addition, a pulmonary function test was also conducted on the MWCNT manufacturing workers (9) and office workers (4). The worker exposure to elemental carbon was found to be 6.2-9.3 µg/m(3) in the personal samplings and 5.5-7.3 µg/m(3) in the area samplings. Notwithstanding, the workers exhibited a normal range of hematology and blood biochemistry values and normal lung function parameters. When analyzing the EBCs, the malondialdehyde (MDA), 4-hydroxy-2-hexenal (4-HHE) and n-hexanal levels in the MWCNT manufacturing workers were significantly higher than those in the office workers. The MDA and n-hexanal levels were also significantly correlated with the blood molybdenum concentration, suggesting MDA, n-hexanal and molybdenum as useful biomarkers of MWCNT exposure.


Assuntos
Indicadores Básicos de Saúde , Exposição por Inalação , Nanotubos de Carbono/toxicidade , Exposição Ocupacional , Saúde Ocupacional , Local de Trabalho/organização & administração , Adulto , Biomarcadores/análise , Feminino , Humanos , Exposição por Inalação/efeitos adversos , Exposição por Inalação/análise , Masculino , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Saúde Ocupacional/normas , Testes de Função Respiratória , Local de Trabalho/normas
19.
Arch Toxicol ; 89(7): 1083-94, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24935253

RESUMO

Gold nanoparticles are known to be distributed to many tissues following their oral, inhalation, or intravenous exposure. Information on the biodistribution and clearance of gold nanoparticles from these tissues is, therefore, important to understand their behavior in vivo. To study the effect of size on the biodistribution of gold nanoparticles, Sprague-Dawley rats were exposed by inhalation to small gold nanoparticles (13 nm in diameter on average) at an exposure concentration of 12.8 ± 2.42 µg/m(3), and to large gold nanoparticles (105 nm in diameter on average) at an exposure concentration of 13.7 ± 1.32 µg/m(3). The experimental animals were exposed to the gold nanoparticles and the control animals to fresh air for 5 days (6 h/day), followed by a recovery period of 1, 3, and 28 days in fresh air. None of the exposed animals exhibited any toxic response to the gold nanoparticles. Despite the difference in size, both small and large gold nanoparticles deposited mainly in rat lungs. Their biodistribution from the lungs to secondary target organs was significantly higher with the small compared to the large gold nanoparticles. While the large gold nanoparticles were only found in the blood, the small gold nanoparticles were detected in the liver, spleen, brain, testes, and blood. In addition, the elimination half-life of the small gold nanoparticles from the lungs was significantly shorter than that of the large gold nanoparticles. The present data may, therefore, suggest that the smaller gold nanoparticles are able to translocate from the lungs, the primary exposure organ to extrapulmonary organs at a faster rate than the larger gold nanoparticles and thus confirming previous observations reported in the literature.


Assuntos
Compostos de Ouro/farmacocinética , Exposição por Inalação , Pulmão/metabolismo , Nanopartículas Metálicas , Aerossóis , Animais , Compostos de Ouro/administração & dosagem , Compostos de Ouro/química , Compostos de Ouro/toxicidade , Meia-Vida , Pulmão/ultraestrutura , Masculino , Taxa de Depuração Metabólica , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Ratos Sprague-Dawley , Medição de Risco , Distribuição Tecidual
20.
Saf Health Work ; 5(2): 91-6, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25180140

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is an important cause of occupational mortality in miners exposed to coal mine dust. Although the inflammatory mediators involved in COPD have not been defined, many studies have shown that inflammatory mediators such as reactive oxygen and nitrogen species are involved in orchestrating the complex inflammatory process in COPD. METHODS: To investigate the relevance of exhaled biomarkers of oxidative and nitrosative stress in participants with COPD, we determined the levels of hydrogen peroxide, malondialdehyde (MDA), and 3-nitrotyrosine (3-NT) in exhaled breath condensate (EBC) in 90 retired elderly coal miners (53 non-COPD and 37 COPD participants). RESULTS: Mean levels of MDA (4.64 nM vs. 6.46 nM, p = 0.005) and 3-NT (3.51 nM vs. 5.50 nM, p = 0.039) in EBC were significantly higher in participants with COPD. The median level of MDA did show statistical difference among the COPD severities (p = 0.017), and the area under the receiver operating characteristic curve for MDA (0.67) for the diagnostic discrimination of COPD indicated the biomarker. The optimal cutoff values were 5.34 nM (64.9% sensitivity and 64.2% specificity) and 5.58 nM (62.2% sensitivity and 62.3% specificity) for MDA and 3-NT, respectively. The results suggest that high levels of MDA and 3-NT in EBC are associated with COPD in retired elderly miners. CONCLUSION: These results showed that the elevated levels of EBC MDA and EBC 3-NT in individuals with COPD are biomarkers of oxidative or nitrosative stress.

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