Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.476
Filtrar
1.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(2): 121-123, 2020 Feb 06.
Artigo em Chinês | MEDLINE | ID: mdl-32074695

RESUMO

This article summarized the use of guanidine disinfectants in China and the use of guanidine cationic disinfectants, polyhexamethylene guanidine (PHMG), in South Korea, which had caused severe lung damage events such as pulmonary fibrosis. The authors reviewed the studies that Chinese scientists employed ultrasonic atomization technology to simulate the actual scenario of human exposure to PHMG and proved the findings that PHMG could cause pulmonary fibrosis. These results could highlight the necessity of full attention to lung damage caused by guanidine disinfectants and its mechanism, so as to provide the important scientific basis for the protection of public health safety and the formulation of corresponding policies.


Assuntos
Desinfetantes/toxicidade , Guanidinas/toxicidade , Pneumopatias/induzido quimicamente , China , Humanos , Fibrose Pulmonar/induzido quimicamente , República da Coreia
2.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(2): 209-212, 2020 Feb 06.
Artigo em Chinês | MEDLINE | ID: mdl-32074712

RESUMO

Polyhexamethylene guanidine (PHMG) is a high molecular guanidine compound with a broad spectrum of antibacterial effects. Since the outbreak of the 'humidifier disinfectant-induced lung injury' event in South Korea, the respiratory toxicity of PHMG had become a public concern. An epidemiological survey in Korea found that PHMG-containing disinfectants were an important risk factor for pulmonary fibrosis. Animal experiments also showed that the exposure to PHMG through the respiratory tract could cause irreversible fibrosis in the lungs. TGF-ß signaling pathway, epithelial-mesenchymal transition and pulmonary inflammation might be the main pathways that could mediate PHMG-induced pulmonary fibrosis. This article provided an overview of the characteristics of population exposure to PHMG and research progress in the field of respiratory toxicology and recommendations for the rational and standard of using PHMG-related products in China.


Assuntos
Desinfetantes/toxicidade , Guanidinas/toxicidade , Pneumopatias/induzido quimicamente , China , Humanos
3.
Monaldi Arch Chest Dis ; 90(1)2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32088948

RESUMO

Diffuse alveolar haemorrhage (DAH) is characterised by diffuse pulmonary opacities, respiratory failure, a falling haemoglobin level along with presence of hemosiderin-laden macrophages on bronchoalveolar lavage (BAL). Finding the underlying aetiology of DAH can be challenging but of importance as the treatment and prognosis are largely determined by it. We report a case of DAH with underlying cocaine abuse, a rare cause for the same.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Hemorragia/induzido quimicamente , Pneumopatias/induzido quimicamente , Humanos , Prognóstico
4.
Chemosphere ; 241: 125087, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31622892

RESUMO

Brominated flame-retardant (BFRs) exposure promotes multiple adverse health outcomes involved in oxidative stress, inflammation, and tissues damage. We investigated BFR effects, known as polybrominated diphenyl ethers (PBDEs) (47, 99 and 209) in an air-liquid-interface (ALI) airway tissue derived from A549 cell line, and compared with ALI culture of primary human bronchial epithelial cells (pHBEC). The cells, exposed to PBDEs (47, 99 and 209) (0.01-1 µM) for 24 h, were studied for IL-8, Muc5AC and Muc5B (mRNAs and proteins) production, as well as NOX-4 (mRNA) expression. Furthermore, we evaluated tight junction (TJ) integrity by Trans-Epithelial Electrical Resistance (TEER) measurements, and zonula occludens-1 (ZO-1) expression in the cells, and pH variations and rheological properties (elastic G', and viscous G″, moduli) in apical washes of ALI cultures. N-acetylcysteine (NAC) (10 mM) effects were tested in our experimental model of A549 cells. PBDEs (47, 99 and 209) exposure decreased TEER, ZO-1 and pH values, and increased IL-8, Muc5AC, Muc5B (mRNAs and proteins), NOX-4 (mRNA), and rheological parameters (G', G″) in ALI cultures of A549 cell line and pHBEC. NAC inhibited PBDE effects in A549 cells. PBDE inhalation might impairs human health of the lungs inducing oxidative stress, inflammatory response, loss of barrier integrity, unchecked mucus production, as well as altered physicochemical and biological properties of the fluids in airway epithelium. The treatment with anti-oxidants restored the negative effects of PBDEs in epithelial cells.


Assuntos
Brônquios/citologia , Éteres Difenil Halogenados/toxicidade , Pneumopatias/induzido quimicamente , Células A549 , Idoso , Impedância Elétrica , Células Epiteliais/efeitos dos fármacos , Retardadores de Chama/toxicidade , Humanos , Interleucina-8/genética , Interleucina-8/metabolismo , Pneumopatias/fisiopatologia , Mucina-5AC/genética , Mucina-5AC/metabolismo , Mucina-5B/genética , Mucina-5B/metabolismo , NADPH Oxidase 4/genética , NADPH Oxidase 4/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/fisiologia
5.
Immunology ; 159(2): 167-177, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31646612

RESUMO

Immune checkpoint inhibition with monoclonal antibodies is becoming increasingly commonplace in cancer medicine, having contributed to a widening of therapeutic options across oncological indications. Disruption of immune tolerance is the key mechanism of action of checkpoint inhibitors and although immune-related adverse events are a typical class effect of these compounds, the relationship between toxicity and response is not fully understood. Awareness and vigilance are paramount in recognizing potentially life-threatening toxicities and managing them in a timely manner. In this review article, we provide an overview of the clinical features, pathological findings and management principles of common immune-related toxicities, attempting to provide mechanistic insight into an increasingly common complication of cancer therapy.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doenças do Sistema Endócrino/induzido quimicamente , Gastroenteropatias/induzido quimicamente , Tolerância Imunológica/efeitos dos fármacos , Imunoterapia/efeitos adversos , Pneumopatias/induzido quimicamente , Terapia de Alvo Molecular/efeitos adversos , Neoplasias/tratamento farmacológico , Animais , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/terapia , Doenças do Sistema Endócrino/imunologia , Doenças do Sistema Endócrino/metabolismo , Doenças do Sistema Endócrino/terapia , Gastroenteropatias/imunologia , Gastroenteropatias/metabolismo , Gastroenteropatias/terapia , Humanos , Pneumopatias/imunologia , Pneumopatias/metabolismo , Pneumopatias/terapia , Neoplasias/imunologia , Neoplasias/metabolismo , Fatores de Risco , Evasão Tumoral/efeitos dos fármacos
6.
Toxicol Lett ; 316: 94-108, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31499141

RESUMO

The toxic effects resulting from inhalation exposure depend on both the concentration (C) of the inhaled substance and the exposure duration (t), including the assumptions that the exposure-limiting toxic effect is linearly linked with the accumulated C × t (inhaled dose), and detoxification or compensatory responses diminishing this dose are negligible. This interrelationship applies for both constant and fluctuating concentrations and is usually expressed by the toxic load equation Cn × t = constant effect (k). The toxic load exponent 'n' is derived from both C- and t-dependent exponents with Cb2×tb3 = k with n = b2/b3. This model is taken as a fundamental basis for assessing the acute hazard posed by atmospheric releases of noxious substances, whether deliberate or accidental. Despite its universal use, especially for inhaled irritants, the toxicological significance of this mathematical construct is still discussed controversially. With n = 1 this equation is called Haber's rule. The underlying assumption is that the exposure-based calculated and the actually inhaled Cb2×tb3 are identical. Unlike the calculated dose, the latter is dependent on the test species and its t-dependent change in respiratory minute volume (MV). The retention patterns of inhaled irritant vapors may differ in obligate nasal breathing rodents and oronasally breathing humans as well. Thus, due to the interdependence of n on both C, t and k, this mathematical construct generates a bioassay-specific 'n' which can hardly be considered as human-equivalent, especially following exposure to sensory irritants known to elicit reflex-related changes in MV. The C- and t-dependent impact on Cn × t = k was analyzed with the sensory irritant n-butyl monoisocyanate and compared with t-dependent changes elicited by highly, moderately, and poorly water-soluble sensory irritants ammonia, toluene diisocyanate, and phosgene, respectively. This comparison reveals that n depends on several factors: In cases where MV is instantly and plateau-like depressed with onset of exposure, n appears to be most dependent on Cb2 × MV whereas for a similar slower time-dependent response n becomes more dependent on MV × tb3. For any ensuing risk characterization that focuses on acute non-lethal threshold Cb2 × tb3's, the sensory irritation-related depression in MV must be known to arrive at meaningful conclusions. In summary, both Cn- and t-dependent dosimetry-related pitfalls may occur in acute bioassays on rodents following inhalation exposure to irritants. These must be identified and dealt with judiciously prior to translation to apparently similar human exposures. By default, extrapolations from one duration to another should start with that Cn × t eliciting the least depression in MV with n = 1.


Assuntos
Exposição por Inalação/efeitos adversos , Irritantes/toxicidade , Pneumopatias/induzido quimicamente , Pulmão/efeitos dos fármacos , Modelos Teóricos , Respiração/efeitos dos fármacos , Limiar Sensorial/efeitos dos fármacos , Amônia/química , Amônia/toxicidade , Animais , Relação Dose-Resposta a Droga , Irritantes/química , Isocianatos/química , Isocianatos/toxicidade , Dose Letal Mediana , Pulmão/fisiopatologia , Pneumopatias/fisiopatologia , Masculino , Camundongos , Fosgênio/química , Fosgênio/toxicidade , Ratos Wistar , Medição de Risco , Solubilidade , Fatores de Tempo , Tolueno 2,4-Di-Isocianato/química , Tolueno 2,4-Di-Isocianato/toxicidade
7.
Diving Hyperb Med ; 49(3): 154-160, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31523789

RESUMO

BACKGROUND: The risk of oxygen toxicity has become a prominent issue due to the increasingly widespread administration of hyperbaric oxygen (HBO) therapy, as well as the expansion of diving techniques to include oxygen-enriched gas mixtures and technical diving. However, current methods used to calculate the cumulative risk of oxygen toxicity during an HBO exposure i.e., the unit pulmonary toxic dose concept, and the safe boundaries for central nervous system oxygen toxicity (CNS-OT), are based on a simple linear relationship with an inspired partial pressure of oxygen (PO2) and are not supported by recent data. METHODS: The power equation: Toxicity Index = t2 × PO2c, where t represents time and c represents the power term, was derived from the chemical reactions producing reactive oxygen species or reactive nitrogen species. RESULTS: The toxicity index was shown to have a good predictive capability using PO2 with a power c of 6.8 for CNS-OT and 4.57 for pulmonary oxygen toxicity. The pulmonary oxygen toxicity index (PO2 in atmospheres absolute, time in h) should not exceed 250. The CNS-OT index (PO2 in atmospheres absolute, time in min) should not exceed 26,108 for a 1% risk. CONCLUSION: The limited use of this toxicity index in the diving community, after more than a decade since its publication in the literature, establishes the need for a handy, user-friendly implementation of the power equation.


Assuntos
Doenças do Sistema Nervoso Central/induzido quimicamente , Oxigenação Hiperbárica , Hiperóxia , Pneumopatias/induzido quimicamente , Oxigênio/toxicidade , Sistema Nervoso Central , Mergulho/fisiologia , Humanos , Oxigenação Hiperbárica/efeitos adversos , Pressão Parcial
8.
Environ Pollut ; 254(Pt A): 112933, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31382213

RESUMO

Exposure to fine atmospheric Particulate Matter (PM) is one of the major environmental causes involved in the development of inflammatory lung diseases, such as chronic obstructive pulmonary disease (COPD) or asthma. When PM is penetrating in the pulmonary system, alveolar macrophages represent the first line of defense, in particular by triggering a pro-inflammatory response, and also by their ability to recruit infiltrating macrophages from the bone marrow. The aim of this in vitro study was to evaluate the gene expression and cytokine production involved in the toxicological and inflammatory responses of infiltrating macrophages, as well as the Extracellular Vesicles (EVs) production, after their exposure to PM. The ability of these EVs to convey information related to PM exposure from exposed macrophages to pulmonary epithelial cells was also evaluated. Infiltrating macrophages respond to fine particles exposure in a conventional manner, as their exposure to PM induced the expression of Xenobiotic Metabolizing Enzymes (XMEs) such as CYP1A1 and CYP1B1, the enzymes involved in oxidative stress SOD2, NQO1 and HMOX as well as pro-inflammatory cytokines in a dose-dependent manner. Exposure to PM also induced a greater release of EVs in a dose-dependent manner. In addition, the produced EVs were able to induce a pro-inflammatory phenotype on pulmonary epithelial cells, with the induction of the release of IL6 and TNFα proinflammatory cytokines. These results suggest that infiltrating macrophages participate in the pro-inflammatory response induced by PM exposure and that EVs could be involved in this mechanism.


Assuntos
Poluentes Atmosféricos/toxicidade , Células Epiteliais/metabolismo , Vesículas Extracelulares/metabolismo , Macrófagos Alveolares/metabolismo , Material Particulado/toxicidade , Poluentes Atmosféricos/metabolismo , Linhagem Celular , Citocinas/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Pulmão/metabolismo , Pneumopatias/induzido quimicamente , Estresse Oxidativo , Tamanho da Partícula , Material Particulado/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
10.
Clin Nucl Med ; 44(9): e519-e521, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31348077

RESUMO

A 57-year-old man with stage IIIB malignant melanoma of unknown primary presented for pretherapy FDG PET/CT that demonstrated metastatic left cervical lymph node with no other site of involvement. Following left neck dissection, nivolumab was initiated. Follow-up FDG PET/CT 3 months after initiation of nivolumab demonstrated extensive radiotracer-avid chest lymphadenopathy and multiple bone lesions. Ultrasound-guided endobronchial biopsy of the mediastinal lymph nodes demonstrated sarcoidosis.


Assuntos
Doenças Ósseas/induzido quimicamente , Pneumopatias/induzido quimicamente , Melanoma/tratamento farmacológico , Neoplasias Primárias Desconhecidas/tratamento farmacológico , Nivolumabe/efeitos adversos , Sarcoidose/induzido quimicamente , Sarcoidose/diagnóstico por imagem , Doenças Ósseas/diagnóstico por imagem , Fluordesoxiglucose F18 , Humanos , Pneumopatias/diagnóstico por imagem , Linfadenopatia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
11.
Chemosphere ; 233: 879-887, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31340414

RESUMO

Epidemiological studies have shown that fine particulate matter (PM2.5) has adverse impacts on human health. However, limited studies have investigated the effects of short-term exposure to PM2.5 and its constituents on mortality in China. This study used the generalized linear model (GLM) to investigate the effects of PM2.5 and its constituents, including organic carbon (OC), element carbon (EC), ammonium (NH4+), nitrate (NO3-), sulfate (SO42-), on different causes of mortality in Shanghai from January 1, 2013 to December 31, 2015. The single-day lagged model and the moving average lagged model were used to examine the lagging effects of pollutants on mortality. At lag0 day, PM2.5 had a significant effect on all-cause mortality, and a 10 µg/m3 increase leads to 0.68% increase in all-cause mortality (RR 1.0068, 95%CI 1.0013-1.0123). Among the five constituents, EC had the greatest impact on all-cause mortality in Shanghai, with 10.48% increase of mortality (RR 1.1048, 95%CI 1.0266-1.1891) per 10 µg/m3 increase of concentrations, followed by OC (RR 1.0577, 95%CI 1.0277-1.0886), NH4+ (RR 1.0272, 95%CI 1.0028-1.0522) and SO42- (RR 1.0104, 95%CI 1.0003-1.0206). For respiratory diseases mortality, EC, OC, NO3- and NH4+ had significant impacts and caused an increase of mortality by 44.99% (RR 1.4499, 95%CI 1.1813-1.7794), 10.40% (RR 1.1040, 95%CI 1.0260-1.1880), 5.338% (RR 1.0533, 95%CI 1.0097-1.0989) and 7.34% (RR 1.0734, 95%CI 1.0015-1.1505) per 10 µg/m3 increase of concentrations, respectively. The cumulative effect of PM2.5 on mortality was significant in Shanghai. Except for SO42-, the RR value of the single-day lagged model was smaller than the moving average lagged model.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/análise , Exposição Ambiental/efeitos adversos , Pneumopatias/induzido quimicamente , Pneumopatias/mortalidade , Material Particulado/análise , Compostos de Amônio/análise , Carbono/análise , China , Humanos , Modelos Lineares , Nitratos/análise , Sulfatos/análise
12.
EBioMedicine ; 45: 553-562, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31204278

RESUMO

BACKGROUND: The Single immunoglobin interleukin-1 (IL-1)-related receptor (Sigirr), also known as IL-1R8, has been shown to exhibit broad anti-inflammatory effects against inflammatory diseases including acute lung injury, while molecular regulation of IL-1R8/Sigirr protein stability has not been reported. This study is designed to determine whether stabilization of IL-1R8/Sigirr by a deubiquitinating enzyme (DUB) is sufficient to suppress inflammatory responses and lessen lung inflammation. METHODS: A molecular signature of ubiquitination and degradation of IL-1R8/Sigirr was determined using a receptor ligation chase model. The anti-inflammatory effects on USP13 were investigated. USP13 knockout mice were evaluated for stabilization of IL-1R8/Sigirr and disease phenotype in an acute lung injury model. FINDINGS: IL-1R8/Sigirr degradation is mediated by the ubiquitin-proteasome system, through site-specific ubiquitination. This effect was antagonized by the DUB USP13. USP13 levels correlate directly with IL-1R8/Sigirr, and both proteins were reduced in cells and tissue from mice subjected to inflammatory injury by the TLR4 agonist lipopolysaccharide (LPS). Knockdown of USP13 in cells increased IL-1R8/Sigirr poly-ubiquitination and reduced its stability, which enhanced LPS-induced TLR4 signaling and cytokine release. Likewise, USP13-deficient mice were highly susceptible to LPS or Pseudomonas aeruginosa models of inflammatory lung injury. IL-1R8/Sigirr overexpression in cells or by pulmonary viral transduction attenuated the inflammatory phenotype conferred by the USP13-/- genotype. INTERPRETATION: Stabilization of IL-1R8/Sigirr by USP13 describes a novel anti-inflammatory pathway in diseases that could provide a new strategy to modulate immune activation. FUND: This study was supported by the US National Institutes of Health (R01HL131665, HL136294 to Y.Z., R01 GM115389 to J.Z.).


Assuntos
Endopeptidases/genética , Pneumopatias/genética , Pneumonia/genética , Receptores de Interleucina-1/genética , Animais , Anti-Inflamatórios/uso terapêutico , Modelos Animais de Doenças , Humanos , Lipopolissacarídeos/uso terapêutico , Pneumopatias/induzido quimicamente , Pneumopatias/patologia , Camundongos , Camundongos Knockout , Pneumonia/induzido quimicamente , Pneumonia/patologia , Pneumonia/terapia , Estabilidade Proteica , Transdução de Sinais/genética , Receptor 4 Toll-Like/genética
13.
Bull Cancer ; 106(9): 805-811, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31171345

RESUMO

Testicular cancers are the most frequent and the most curable cancers in young men. Treatments of these cancers represent a great success with cure rate over to 95 %. However, chemotherapy side effects may occur during or after several years post-treatment. This review aimed to highlight complications and physical and psychological side effects occurring mainly after chemotherapy treatment for testicular cancer, and to propose a personalized post-cancer plan specific for patients treated for testicular cancer. Treatments of these cancers can cause short-term complications (asthenia, nausea, vomiting, alopecia..). These side effects disappear within a few months after the end of the treatments. Late complications may occur several years post-treatment. Cardiovascular disease, metabolic syndrome and secondary neoplasia represent the most severe late effects among patients treated for testicular cancer. Given the increased incidence of these chemotherapy-induced side effects, it is indispensable to establish a specific follow up which must include a particular vigilance on the risk of occurrence of second cancer, a follow-up of the cardio-vascular risk factors, pulmonary and auditory follow-up, and early detection of psychosocial disorders.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias Testiculares/tratamento farmacológico , Doenças Cardiovasculares/induzido quimicamente , Cognição/efeitos dos fármacos , Transtornos Cognitivos/induzido quimicamente , Síndrome de Fadiga Crônica/induzido quimicamente , Fertilidade/efeitos dos fármacos , Seguimentos , Humanos , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/prevenção & controle , Pneumopatias/induzido quimicamente , Masculino , Síndrome Metabólica/induzido quimicamente , Segunda Neoplasia Primária/induzido quimicamente , Doenças do Sistema Nervoso/induzido quimicamente , Neoplasias Testiculares/psicologia , Fatores de Tempo
14.
Environ Pollut ; 252(Pt B): 1216-1224, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31252119

RESUMO

The effects of methylamine on human health have been debated for several years, but the exact adverse outcomes and definite signaling cascades have not been elucidated yet. Herein, a NF-κB signal pathway, a positive regulator of inflammation was identified as the main pathway of methylamine exposure induced adverse effects in bronchial airway cells (16HBE) for the first time. The results indicated that methylamine could stimulate the overproduction of reactive oxygen species (ROS) in cytoplasm and mitochondria of 16HBE cells. Moreover, ROS accelerate the translocation and phosphorylation of NF-κB in nucleic and promote the expression of inflammatory, such as IL-8 and IL-6. As a result, methylamine was found to be increased ROS-mediated NF-κB activation in cells, leading to the production of inflammatory cytokine. Furthermore, the results also showed that methylamine could affect the expression of cytokines related genes, p53, STAT3, Bcl2, c-myc, Cyclin D, Hes1, Mcl-1, TGF-ß2. The breakdown of those cell proliferation and apoptosis related genes were leading to a common toxic mechanism of cell death. In summary, our work uncovers a mechanism by which methylamine can induce the formation of inflammation response and demonstrates potential inflammation and carcinogenesis in human airway cell upon the methylamine inhaled.


Assuntos
Poluentes Atmosféricos/toxicidade , Exposição Ambiental/efeitos adversos , Inflamação/patologia , Pneumopatias/induzido quimicamente , Metilaminas/toxicidade , Fator de Transcrição RelA/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Regulação da Expressão Gênica , Humanos , Interleucina-6/biossíntese , Interleucina-8/biossíntese , Mitocôndrias/metabolismo , Fosforilação , Transporte Proteico/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos
15.
Iran J Allergy Asthma Immunol ; 18(2): 218-224, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31066258

RESUMO

The mustard lung is a late consequence of exposure to sulfur mustard (SM) in veterans who had participated in the Iraq-Iran war. Three mechanisms are contributed in the pathogenesis of mustard lung including oxidative stress, protease-antiprotease imbalance, and dysregulated immune response. In the context of the immune response, the role of the inflammasome complex and their inflammatory cytokines are important. This study aims to investigate the inflammasome pathway and their inflammatory cytokine (i.e IL-1 and IL-18) in the peripheral blood of mustard lung patients as well as chronic obstructive pulmonary disease (COPD) patients. This research was conducted as a cross-sectional analytical study on 15 SM patients and was compared with 15 COPD patients and 15 healthy controls. The real-time polymerase chain reaction was used to assess gene expression levels of inflammasome components (NLRP1, NLRP3, NLRC4, and ASC), inflammatory cytokines (IL-1ß, IL-18, and IL-1ßR), and IL-37 as an anti-inflammatory cytokine. Finally, the data were analyzed by SPSS version 21 software. The gene expression level of molecules involved in inflammasome pathway showed a slight increase in the peripheral blood of SM and COPD patients compared to the control group. However, this difference was not statistically significant. Only IL-37 and NLRP1 had a significant increase in mustard lung and COPD patients; compared to healthy controls (p<0.05). Due to the normal expression of genes involved in the inflammasome pathway, it can be stated that the inflammasome pathway is not active in the blood of mustard lung patients.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Substâncias para a Guerra Química/efeitos adversos , Inflamassomos/metabolismo , Interleucina-1/metabolismo , Pneumopatias/imunologia , Gás de Mostarda/efeitos adversos , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose/genética , Estudos Transversais , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Mediadores da Inflamação/sangue , Interleucina-1/sangue , Interleucina-1/genética , Interleucina-18/sangue , Guerra do Iraque 2003-2011 , Pneumopatias/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/imunologia , Veteranos
16.
Toxicol Lett ; 312: 188-194, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31095986

RESUMO

Sulfur mustard (SM) is a toxic agent that causes acute and long-term pulmonary complications. Recent evidence has shown the impact of SM on mesenchymal stem cells (MSCs). These cells have a critical role in repairing the damaged tissues. In this study, we evaluated the mobilization of MSCs in SM-exposed patients with long-term pulmonary complications. Fifty-nine SM-injured patients with prolonged pulmonary complications and 20 healthy individuals were included. Patients were classified based on taking drugs, having comorbidities, and severity of respiratory consequence. MSCs with phenotype of CD45-CD44+CD29+CD105+ were evaluated in peripheral blood using flow cytometry. Circulating MSCs were lower in SM-exposed patients compared to the control group (0.93 vs. 2.72 respectively, P = 0.005). No significant difference was observed in the MSC count between patients taking corticosteroids or antibiotics and those patients not taking them. Comorbidities like liver and kidney diseases had changed the count of MSCs in SM-exposed subjects. In addition, the frequency of MSCs did not show any association with the severity of long-term pulmonary complications. In conclusion, SM-exposure causes a decline in the frequency of circulating MSCs in survivors. The lower number of the peripheral MSC population in SM-exposed patients was not affected by taking corticosteroids or antibiotics, but comorbidities are probably involved in MSC frequency. The decreases observed in the number of circulating MSCs was not associated with the severity of the pulmonary complications; however, further studies in mustard lung models are required to demonstrate the therapeutic or pathologic role of MSCs in SM injuries.


Assuntos
Substâncias para a Guerra Química/toxicidade , Pneumopatias/induzido quimicamente , Células-Tronco Mesenquimais/efeitos dos fármacos , Gás de Mostarda/toxicidade , Adulto , Feminino , Humanos , Irã (Geográfico) , Pneumopatias/patologia , Masculino , Pessoa de Meia-Idade
19.
Inhal Toxicol ; 31(1): 25-34, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30997849

RESUMO

The distribution of dust particles within the lungs and their excretion are highly associated with their pulmonary toxicity. Literature was reviewed to discern pulmonary translocation pathways for inhaled α-quartz compared to those for inhaled TiO2. Accordingly, it was hypothesized α-quartz particles in the alveoli were phagocytized by alveolar macrophages but silica-containing macrophages remained in the alveoli for longer time in contrast to the rapid elimination from the alveoli seen for TiO2-containing macrophages. In addition, it was presumed that free silica particles are translocated in the interstitium, possibly through the cytoplasm of Type I epithelial cells, as observed with TiO2. Free silica particles are presumed to be phagocytized by interstitial macrophages soon after the particles penetrate the interstitium; these dust cells are then translocated to the ciliated airway regions in the lumen through bronchus-associated lymphoid tissue (BALT). The pulmonary retention half-time of dust particles in rats exposed to α-quartz is several times longer than that of rats exposed to TiO2, as long as the lung dust burden is ≈ 3 mg. The reduced pulmonary particle clearance ability in rats exposed to α-quartz aerosol is presumably attributed to the long-term retention of dust cells both in the alveoli and in the interstitium; this retention may be caused by the reduced chemotactic abilities of α-quartz-containing dust cells. However, the accumulation of α-quartz-containing dust cells in the lungs is not associated with the occurrence of pulmonary inflammation.


Assuntos
Pulmão/metabolismo , Quartzo/farmacocinética , Administração por Inalação , Animais , Granuloma/induzido quimicamente , Pulmão/efeitos dos fármacos , Pneumopatias/induzido quimicamente , Linfonodos/metabolismo , Quartzo/toxicidade , Ratos
20.
Medicine (Baltimore) ; 98(8): e14626, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30813195

RESUMO

RATIONALE: Diffuse alveolar hemorrhage (DAH) is a rare life-threatening condition that accompanies general anesthesia. Negative-pressure pulmonary edema (NPPE) is a rare cause of DAH. PATIENT CONCERNS: A 25-year-old male patient developed hemoptysis following remifentanil administration by bolus injection with sugammadex at the emergence from general anesthesia. DIAGNOSIS: Chest x-ray and computed tomography showed DAH. INTERVENTIONS: Conservative care was provided with 4L of oxygen via nasal prong, 20 mg of Lasix and 2500 mg of tranexamic acid. OUTCOMES: The patient was discharged uneventfully. LESSONS: Muscle rigidity by remifentanil and the dissociated reversal of neuromuscular blockade by sugammadex was suspected as the cause of NPPE-related DAH. Therefore, the possibility NPPE-related DAH should be considered when using a bolus of remifentanil and sugammadex during emergence from general anesthesia.


Assuntos
Hemorragia/induzido quimicamente , Pneumopatias/induzido quimicamente , Edema Pulmonar/induzido quimicamente , Remifentanil/efeitos adversos , Sugammadex/efeitos adversos , Adulto , Analgésicos Opioides/efeitos adversos , Anestesia Geral/efeitos adversos , Hemoptise/etiologia , Humanos , Pulmão/patologia , Masculino , Edema Pulmonar/complicações , Tomografia Computadorizada por Raios X
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA