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2.
Anesthesiology ; 132(2): 307-320, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31939846

RESUMO

BACKGROUND: Pressure-support ventilation may worsen lung damage due to increased dynamic transpulmonary driving pressure. The authors hypothesized that, at the same tidal volume (VT) and dynamic transpulmonary driving pressure, pressure-support and pressure-controlled ventilation would yield comparable lung damage in mild lung injury. METHODS: Male Wistar rats received endotoxin intratracheally and, after 24 h, were ventilated in pressure-support mode. Rats were then randomized to 2 h of pressure-controlled ventilation with VT, dynamic transpulmonary driving pressure, dynamic transpulmonary driving pressure, and inspiratory time similar to those of pressure-support ventilation. The primary outcome was the difference in dynamic transpulmonary driving pressure between pressure-support and pressure-controlled ventilation at similar VT; secondary outcomes were lung and diaphragm damage. RESULTS: At VT = 6 ml/kg, dynamic transpulmonary driving pressure was higher in pressure-support than pressure-controlled ventilation (12.0 ± 2.2 vs. 8.0 ± 1.8 cm H2O), whereas static transpulmonary driving pressure did not differ (6.7 ± 0.6 vs. 7.0 ± 0.3 cm H2O). Diffuse alveolar damage score and gene expression of markers associated with lung inflammation (interleukin-6), alveolar-stretch (amphiregulin), epithelial cell damage (club cell protein 16), and fibrogenesis (metalloproteinase-9 and type III procollagen), as well as diaphragm inflammation (tumor necrosis factor-α) and proteolysis (muscle RING-finger-1) were comparable between groups. At similar dynamic transpulmonary driving pressure, as well as dynamic transpulmonary driving pressure and inspiratory time, pressure-controlled ventilation increased VT, static transpulmonary driving pressure, diffuse alveolar damage score, and gene expression of markers of lung inflammation, alveolar stretch, fibrogenesis, diaphragm inflammation, and proteolysis compared to pressure-support ventilation. CONCLUSIONS: In the mild lung injury model use herein, at the same VT, pressure-support compared to pressure-controlled ventilation did not affect biologic markers. However, pressure-support ventilation was associated with a major difference between static and dynamic transpulmonary driving pressure; when the same dynamic transpulmonary driving pressure and inspiratory time were used for pressure-controlled ventilation, greater lung and diaphragm injury occurred compared to pressure-support ventilation.


Assuntos
Diafragma/lesões , Diafragma/fisiopatologia , Lesão Pulmonar/etiologia , Lesão Pulmonar/fisiopatologia , Respiração com Pressão Positiva/efeitos adversos , Respiração com Pressão Positiva/métodos , Animais , Masculino , Respiração com Pressão Positiva/normas , Ratos , Ratos Wistar , Mecânica Respiratória/fisiologia , Volume de Ventilação Pulmonar/fisiologia
3.
J Trauma Acute Care Surg ; 88(2): 310-313, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31389914

RESUMO

BACKGROUND: There are no reports comparing wounding pattern in urban and public mass shooting events (CPMS). Because CPMS receive greater media coverage, there is a connation that the nature of wounding is more grave than daily urban gun violence. We hypothesize that the mechanism of death following urban gunshot wounds (GSWs) is the same as has been reported following CPMS. METHODS: Autopsy reports of all firearm-related deaths in Washington, DC were reviewed from January 1, 2016, to December 31, 2017. Demographic data, firearm type, number and anatomic location of GSWs, and organ(s) injured were abstracted. The organ injury resulting in death was noted. The results were compared with a previously published study of 19 CPMS events involving 213 victims. RESULTS: One hundred eighty-six urban autopsy reports were reviewed. There were 171 (92%) homicides and 13 (7%) suicides. Handguns were implicated in 180 (97%) events. One hundred eight (59%) gunshots were to the chest/upper back, 85 (46%) to the head, 77 (42%) to an extremity, and 71 (38%) to the abdomen/lower back. The leading mechanisms of death in both urban firearm violence and CPMS were injury to the brain, lung parenchyma, and heart. Fatal brain injury was more common in CPMS events as compared with urban events involving a handgun. CONCLUSION: There is little difference in wounding pattern between urban and CPMS firearm events. Based on the organs injured, rapid point of wounding care and transport to a trauma center remain the best options for mitigating death following all GSW events. LEVEL OF EVIDENCE: Epidemiological, level IV.


Assuntos
Lesões Encefálicas/mortalidade , Traumatismos Cardíacos/mortalidade , Lesão Pulmonar/mortalidade , Incidentes com Feridos em Massa/estatística & dados numéricos , Ferimentos por Arma de Fogo/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Lesões Encefálicas/etiologia , Lesões Encefálicas/terapia , Causas de Morte , District of Columbia/epidemiologia , Feminino , Traumatismos Cardíacos/etiologia , Traumatismos Cardíacos/terapia , Humanos , Lesão Pulmonar/etiologia , Lesão Pulmonar/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Transporte de Pacientes/estatística & dados numéricos , Centros de Traumatologia/estatística & dados numéricos , Ferimentos por Arma de Fogo/etiologia , Ferimentos por Arma de Fogo/terapia , Adulto Jovem
4.
Radiat Res ; 193(2): 171-185, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31877256

RESUMO

Radiation-induced lung injury (RILI) is a common and severe side effect of thoracic radiotherapy, which compromises patients' quality of life. Recent studies revealed that early vascular injury, especially microvascular damage, played a central role in the development of RILI. For this reason, early vascular protection is essential for RILI therapy. The ATP-sensitive K+ (KATP) channel is an ATP-dependent K+ channel with multiple subunits. The protective role of the KATP channel in vascular injury has been demonstrated in some published studies. In this work, we investigated the effect of KATP channel on RILI. Our findings confirmed that the KATP channel blocker glibenclamide, rather than the KATP channel opener pinacidil, remitted RILI, and in particular, provided protection against radiation-induced vascular injury. Cytology experiments verified that glibenclamide enhanced cell viability, increased the potential of proliferation after irradiation and attenuated radiation-induced apoptosis. Involved mechanisms included increased Ca2+ influx and PKC activation, which were induced by glibenclamide pretreatment. In conclusion, the KATP channel blocker glibenclamide remitted RILI and inhibited the radiation-induced apoptosis of vascular endothelial cells by increased Ca2+ influx and subsequent PKC activation.


Assuntos
Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Glibureto/farmacologia , Canais KATP/antagonistas & inibidores , Lesão Pulmonar/prevenção & controle , Proteína Quinase C/metabolismo , Lesões Experimentais por Radiação/prevenção & controle , Animais , Apoptose/efeitos da radiação , Transporte Biológico/efeitos dos fármacos , Transporte Biológico/efeitos da radiação , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/efeitos da radiação , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/efeitos da radiação , Humanos , Lesão Pulmonar/etiologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Fosforilação/efeitos da radiação , Bloqueadores dos Canais de Potássio/farmacologia , Lesões Experimentais por Radiação/metabolismo , Lesões Experimentais por Radiação/patologia , Pneumonite por Radiação/prevenção & controle
6.
S D Med ; 72(10): 446-449, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31816204

RESUMO

Vaping has recently gained popularity among teenagers and young adults, well beyond its scope as an alterna- tive to cigarette smoking. A perceived favorable safety profile may have stemmed from the fact that vaping is being evaluated as a smoking cessation tool. We present a case of a young adult non-smoker who was exposed to commercially available vaping, and socially available cannabinoid by vaporizer, one to two weeks prior to developing respiratory and constitutional symptoms. His work-up confirmed a case of vaping induced lung injury.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Lesão Pulmonar , Abandono do Hábito de Fumar , Vaping , Adolescente , Humanos , Lesão Pulmonar/epidemiologia , Lesão Pulmonar/etiologia , Nebulizadores e Vaporizadores , Vaping/efeitos adversos , Adulto Jovem
7.
Ann Agric Environ Med ; 26(4): 672-673, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31885245

RESUMO

INTRODUCTION: Thiram, a fungicides, is widely used on seeds and as foliar agent on turf, vegetables and fruit. It is also used in the rubber industry as a vulcanization accelerator. When absorbed through the respiratory system, it is rapidly metabolised to dimethylthiocarbamate and carbon disulphide, causing noxious effects. A brief review is presented of the literature, centering on the interesting case of a 45-year-old woman admitted to the hospital suffering from acute respiratory failure. RESULTS: Computer tomography in angiographic option (angio-CT) showed an extensive, irregular area of ground glass in both upper lobes and apical segments of the lower lobes of the lungs. A significant enlargement of both atria was also described. There was no improvement after cardiac treatment and patient was transferred to the pulmonary department where she was succesfully treated with systemic glucocortycosteroids. The patient remains under the supervision of the pulmonary out-patient department.


Assuntos
Fungicidas Industriais/toxicidade , Exposição por Inalação/efeitos adversos , Lesão Pulmonar/etiologia , Tiram/toxicidade , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/efeitos dos fármacos , Lesão Pulmonar/diagnóstico por imagem , Pessoa de Meia-Idade
8.
Int J Mol Sci ; 20(19)2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31569732

RESUMO

Bronchopulmonary dysplasia (BPD), caused by hyperoxia in newborns and infants, results in lung damage and abnormal pulmonary function. However, the current treatments for BPD are steroidal and pharmacological therapies, which cause neurodevelopmental impairment. Treatment with umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) is an efficient alternative approach. To prevent pulmonary inflammation in BPD, this study investigated the hypothesis that a key regulator was secreted by MSCs to polarize inflammatory macrophages into anti-inflammatory macrophages at inflammation sites. Lipopolysaccharide-induced macrophages co-cultured with MSCs secreted low levels of the inflammatory cytokines, IL-8 and IL-6, but high levels of the anti-inflammatory cytokine, IL-10. Silencing decorin in MSCs suppressed the expression of CD44, which mediates anti-inflammatory activity in macrophages. The effects of MSCs were examined in a rat model of hyperoxic lung damage. Macrophage polarization differed depending on the levels of decorin secreted by MSCs. Moreover, intratracheal injection of decorin-silenced MSCs or MSCs secreting low levels of decorin confirmed impaired alveolarization of damaged lung tissues by down-regulation of decorin. In tissues, a decrease in the anti-inflammatory macrophage marker, CD163, was observed via CD44. Thus, we identified decorin as a key paracrine factor, inducing macrophage polarization via CD44, a master immunoregulator in mesenchymal stem cells.


Assuntos
Decorina/biossíntese , Sangue Fetal/citologia , Receptores de Hialuronatos/sangue , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Animais , Biomarcadores , Modelos Animais de Doenças , Imunofluorescência , Técnicas de Silenciamento de Genes , Humanos , Hiperóxia/complicações , Lesão Pulmonar/diagnóstico , Lesão Pulmonar/etiologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/terapia , Ratos
9.
Am J Chin Med ; 47(6): 1237-1251, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31495180

RESUMO

Inhalation of fine particulate matter (PM2.5) is associated with elevated pulmonary injury caused by the loss of vascular barrier integrity. Black ginseng (BG), steamed and dried ginseng nine times, exhibits various pharmacological activities such as antibacterial, antihyperglycemic, anti-atopic, antibacterial, and anti-inflammatory activities. In this study, we investigated the beneficial effects of black ginseng extract (BGE) against PM-induced lung endothelial cell (EC) barrier disruption and pulmonary inflammation. Permeability, leukocyte migration, activation of proinflammatory proteins, generation of reactive oxygen species (ROS), and histology were examined in PM2.5-treated ECs and mice. BGE significantly scavenged PM2.5-induced ROS and inhibited the ROS-induced activation of p38 mitogen-activated protein kinase (MAPK). Concurrently, BGE activated Akt, which helped maintain endothelial integrity. Furthermore, BGE reduced vascular protein leakage, leukocyte infiltration, and proinflammatory cytokine release in the bronchoalveolar lavage fluid in PM-induced lung tissues. These results indicated that BGE may exhibit protective effects against PM-induced inflammatory lung injury and vascular hyperpermeability.


Assuntos
Lesão Pulmonar/etiologia , Lesão Pulmonar/prevenção & controle , Panax/química , Material Particulado/efeitos adversos , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Animais , Permeabilidade Capilar/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Masculino , Camundongos Endogâmicos BALB C , Extratos Vegetais/isolamento & purificação , Pneumonia/etiologia , Pneumonia/prevenção & controle , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
10.
Life Sci ; 233: 116741, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31398419

RESUMO

AIMS: Carbon black nanoparticles (CBNPs) are widely used in industrial field. Sensitive stages such as pregnancy are assumed to be more susceptible to stimulus, however whether pregnancy exposure to CBNPs (PrE-to-CBNPs) would cause long-term toxic effects in dams and the underlying mechanisms remain poorly addressed. The present study is aimed to determine the long-term toxic effects of PrE-to-CBNPs in dams. MATERIALS AND METHODS: The pregnant mice were randomly divided into control group, low (21 µg/animal), medium (103 µg/animal) and high (515 µg/animal) CBNPs-treated groups. From gestational day (GD) 9 to GD18, the pregnant mice were intranasal exposed. At 49 days after parturition, lung tissues and bronchoalveolar lavage fluid (BALF) were obtained. Weight change, lung histopathology, lung ultrastructural pathology, cell count in BALF, oxidative stress/inflammatory maker and autophagy/lysosome-related protein expression were determined. KEY FINDINGS: PrE-to-CBNPs caused a dose-dependent persistent lung injury in mice even 49 days after parturition, including the deteriorative lung histopathological changes, elevation of oxidative stress marker Nrf-2, HO-1 and CHOP, infiltration of macrophage and increased mRNA expression of inflammatory cytokines in the lung tissues and elevation of cells in BALF. However, PrE-to-CBNPs did not induce significant neutrophil infiltration and fibrosis. Moreover, we found that CBNPs could deposit in the lysosomes and decrease cathepsin D (an important hydrolase in lysosome), which might be associated with the dysfunction of lysosome and autophagy. SIGNIFICANCE: Our study demonstrated that PrE-to-CBNPs could result in long-term lung injury in dams, and lysosomal dysfunction was probably linked to this process.


Assuntos
Inflamação/complicações , Lesão Pulmonar/etiologia , Lisossomos/patologia , Nanopartículas/efeitos adversos , Estresse Oxidativo , Efeitos Tardios da Exposição Pré-Natal/etiologia , Fuligem/efeitos adversos , Animais , Autofagia , Citocinas/metabolismo , Feminino , Lesão Pulmonar/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Efeitos Tardios da Exposição Pré-Natal/patologia
11.
Med Sci Monit ; 25: 6074-6084, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31411185

RESUMO

BACKGROUND Bronchopulmonary dysplasia (BPD) is a major complication of extreme prematurity, characterized by alveolar simplification and pulmonary malfunction. Hyperoxia-induced lung injury in neonatal rats has been used as a model of BPD, as indicated by lung architectural change and alveolar simplification that resembles clinical feature of BPD. ß-defensin-2 (BD2) plays an important role in lung diseases by inhibiting inflammation response. However, little is known about its role in BPD. The aim of this study was to determine the effect of human BD2 (hBD2) gene on hyperoxia-induced animal model of BPD. MATERIAL AND METHODS The neonatal rats were exposed to 90% oxygen (O2) continuously for 14 days to mimic the BPD-like lung injury. These rats were then randomly assigned to the following four groups: in room air (air), in 90% O2, in 90% O2 with null adenovirus vector infection (O2+Ad), and in 90% O2 with gene therapy through adenovirus transfected hBD2 (O2+Ad-hBD2). Morphology of lungs, pulmonary function and expression of inflammatory cytokines on P7, P10, P14, and P21 were documented and compared across the 4 groups. RESULTS The overexpression of hBD2 mediated by the adenovirus vector was successfully constructed. hBD2 gene therapy increased hBD2 mRNA expression, increased radial alveolar count (RAC), lung volume and compliance, decreased mean linear intercept (MLI), tissue damping, and elastance. Furthermore, pro-inflammatory cytokines IL-1ß, IL-6, and TNF-alpha were inhibited and anti-inflammatory cytokines IL-10 was increased in the lungs of rats in O2+Ad-hBD2 group. CONCLUSIONS In hyperoxia-induced rat models of BPD, hBD2 promotes alveolarization and improves pulmonary function. The mechanism may contribute in alleviating inflammation response and inhibiting pro-inflammatory factors including IL-1ß, IL-6, and TNF-alpha.


Assuntos
Lesão Pulmonar/terapia , beta-Defensinas/metabolismo , Animais , Animais Recém-Nascidos , Displasia Broncopulmonar/fisiopatologia , Modelos Animais de Doenças , Feminino , Humanos , Hiperóxia/complicações , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Pulmão/fisiopatologia , Lesão Pulmonar/etiologia , Oxigênio/metabolismo , Gravidez , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo , beta-Defensinas/fisiologia
12.
Braz J Cardiovasc Surg ; 34(4): 436-443, 2019 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-31454197

RESUMO

OBJECTIVE: To investigate the effect of continuous lung ventilation with low tidal volume on oxidation parameters, such as thiol/disulphide homeostasis and albumin-adjusted ischemia-modified albumin (AAIMA), during cardiopulmonary bypass (CBP) in coronary artery bypass grafting (CABG). METHODS: Seventy-four patients who underwent elective CABG with CPB were included in the study. Blood samples were taken in the preoperative period, 10 minutes after CPB, and six and 24 hours postoperatively. Patients were assigned to the continuous ventilation group (Group 1, n=37) and the non-ventilated group (Group 2, n=37). The clinical characteristics, thiol/disulphide homeostasis, ischemia-modified albumin (IMA), and AAIMA levels of the patients were compared. RESULTS: A significant difference was found between the groups regarding native thiol, total thiol, and IMA levels at the postoperative 24th hour (P=0.030, P=0.031, and P=0.004, respectively). There was no difference between the groups in terms of AAIMA. AAIMA levels returned to preoperative levels in Groups 1 and 2, at the 6th and 24th postoperative hours, respectively. Length of hospital stay was significantly shorter in Group 1 (P<0.001) than in Group 2. CONCLUSION: Continuous ventilation during CPB caused an increase in native and total thiol levels, an earlier return of AAIMA levels, and shorter hospital stay. Continuous ventilation may reduce the negative effects of CPB on myocardium (Table 2, Figure 1, and Reference 31).


Assuntos
Ponte Cardiopulmonar/efeitos adversos , Dissulfetos/sangue , Respiração Artificial , Albumina Sérica/análise , Compostos de Sulfidrila/sangue , Idoso , Antioxidantes , Biomarcadores/sangue , Ponte Cardiopulmonar/métodos , Ponte de Artéria Coronária , Método Duplo-Cego , Feminino , Homeostase/fisiologia , Humanos , Lesão Pulmonar/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Albumina Sérica Humana
14.
Redox Biol ; 26: 101264, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31279222

RESUMO

The association between airborne fine particulate matter (PM2.5) concentration and the risk of respiratory diseases has been well documented by epidemiological studies. However, the mechanism underlying the harmful effect of PM2.5 has not been fully understood. In this study, we exposed the C57BL/6J mice to airborne PM2.5 for 3 months (mean daily concentration ~50 or ~110 µg/m3, defined as PM2.5-3L or PM2.5-3H) or 6 months (mean daily concentration ~50 µg/m3, defined as PM2.5-6L) through a whole-body exposure system. Histological and biochemical analysis revealed that PM2.5-3H exposure caused more severe lung injury than did PM2.5-3L, and the difference was greater than that of PM2.5-6L vs PM2.5-3L exposure. With RNA-sequencing technique, we found that the lungs exposed with different concentration of PM2.5 have distinct transcriptional profiles. PM2.5-3H exposure caused more differentially expressed genes (DEGs) in lungs than did PM2.5-3L or PM2.5-6L. The DEGs induced by PM2.5-3L or PM2.5-6L exposure were mainly enriched in immune pathways, including Hematopoietic cell lineage and Cytokine-cytokine receptor interaction, while the DEGs induced by PM2.5-3H exposure were mainly enriched in cardiovascular disease pathways, including Hypertrophic cardiomyopathy and Dilated cardiomyopathy. In addition, we found that upregulation of Cd5l and reduction of Hspa1 and peroxiredoxin-4 was associated with PM2.5-induced pulmonary inflammation and oxidative stress. These results may provide new insight into the cytotoxicity mechanism of PM2.5 and help to development of new strategies to attenuate air pollution associated respiratory disease.


Assuntos
Exposição Ambiental/efeitos adversos , Lesão Pulmonar/etiologia , Material Particulado/efeitos adversos , Animais , Biomarcadores , Suscetibilidade a Doenças , Perfilação da Expressão Gênica , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Masculino , Camundongos , Estresse Oxidativo , Fatores de Tempo , Transcriptoma
15.
Oxid Med Cell Longev ; 2019: 8526083, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31178975

RESUMO

The prevalence of waterpipe (shisha) tobacco smoking has recently seen a substantial increase worldwide and is becoming a public health problem. Both human and animal studies have established that waterpipe smoke (WPS) increases airway reactivity and inflammation. Gum Arabic (GA) is a prebiotic agent that possesses antioxidant and anti-inflammatory properties. However, its effects on lung toxicity induced by WPS exposure are unknown. Thus, the aim of this study was to investigate the possible salutary effects and underlying mechanisms of GA on WPS-induced pulmonary pathophysiologic effects. C57BL/6 mice were exposed to air or WPS (30 minutes/day for one month) with or without GA treatment in drinking water (15%, w/v). Exposure to WPS induced an influx of neutrophil polymorphs in the peribronchiolar and interstitial spaces and an increase of tumor necrosis factor-α and 8-isoprostane, a marker of lipid peroxidation, concentrations in lung homogenates. The latter effects were significantly mitigated by GA treatment. Likewise, the lung DNA damage induced by WPS exposure was prevented by GA administration. Western blot analysis of the lung showed that GA inhibited nuclear factor kappa-B (NF-κB) expression caused by WPS and augmented that of nuclear factor erythroid 2-related factor 2 (Nrf2). Similarly, immunohistochemical analysis of bronchial epithelial cells and alveolar cells showed a parallel and significant increase in the nuclear expression of Nrf2 and cytoplasmic expression of glutathione in mice treated with GA and exposed to WPS. Moreover, GA administration has significantly prevented airway hyperreactivity to methacholine induced by WPS. We conclude that GA administration significantly declined the physiological, histological, biochemical, and molecular indices of lung toxicity caused by WPS exposure, indicating its beneficial respiratory impact. Considering that GA is a safe agent with health benefits in humans, our data suggest its potential usage in waterpipe smokers.


Assuntos
Goma Arábica/uso terapêutico , Lesão Pulmonar/etiologia , Fumaça/efeitos adversos , Cachimbos de Água/normas , Animais , Goma Arábica/farmacologia , Lesão Pulmonar/patologia , Camundongos
16.
Int J Mol Med ; 44(2): 725-736, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173181

RESUMO

The one­lung ventilation (OLV) technique is vital in thoracic surgery. However, it can result in severe lung injury, which is difficult to manage. The main solution at present is the use of ventilation strategies, including continuous positive oxygen pressure, low tidal volume and high frequency ventilation, and the administering of drugs, including phenylephrine, dexmedetomidine and morphine. However, the protective effect of these methods on the lungs is not sufficient to improve the prognosis of patients. Therefore, how to develop a novel protective drug remains an open question. Nicorandil, a mitochondrial (mito)KATP­specific opener, serves an important role in cardioprotection, although its effect on lung injury remains unclear. The present study examined the protective role of nicorandil against collapse­induced lung injury in rabbits undergoing OLV. Changes in arterial oxygen saturation (SaO2), arterial partial pressure for oxygen (PaO2), wet/dry weight ratio, and the microstructure of tissues and cells were observed. Enzyme­linked immunosorbent assays were used to determine the concentrations of malondialdehyde (MDA) and tumor necrosis factor (TNF)­α, and the activity of superoxide dismutase (SOD) in rabbits treated with nicorandil. Terminal deoxynucleotidyl transferase transfer­mediated dUTP nick end­labeling was used to detect apoptosis and western blotting was used to analyze the relative proteins involved in apoptosis. Western blotting and reverse transcription­quantitative polymerase chain reaction analysis were used to examine the expression of hypoxia inducible factor 1α (HIF­1α), phosphatidylinositol­3­kinase (PI3K), protein kinase B (Akt) and nuclear factor (NF)­κB in the lungs of rabbits treated with nicorandil. The SaO2 and PaO2 in the high­dose group were significantly higher than those in the control group in the process of OLV. The wet/dry weight ratio, and the concentrations of MDA and TNF­α in the collapsed lung of the high­dose group were significantly lower than those in the control group. The activity of SOD in the high­dose group was significantly higher than that in the control group. The lung had improved microstructure and less apoptosis, which was determined by the Bax/Bcl2 ratio in the high­dose group. The expression levels of PI3K, phosphorylated Akt and HIF­1α were upregulated, whereas the expression of NF­κB was downregulated. In conclusion, nicorandil had a protective effect via inhibiting apoptosis in non­ventilated lung collapsed and re­expansion during OLV in the rabbit. It acted on mitoKATP through the PI3K/Akt signaling pathway.


Assuntos
Apoptose/efeitos dos fármacos , Lesão Pulmonar/tratamento farmacológico , Nicorandil/uso terapêutico , Substâncias Protetoras/uso terapêutico , Animais , Feminino , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Lesão Pulmonar/etiologia , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Masculino , Nicorandil/farmacologia , Ventilação Monopulmonar/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Coelhos
17.
Biomed Pharmacother ; 117: 109043, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31238259

RESUMO

Sepsis is a severe, life-threatening condition primarily caused by the cellular response to infection. Sepsis leads to increased tissue damage and mortality in patients in the intensive care unit. L-Lysine is an essential amino acid required for protein biosynthesis and is abundant in lamb, pork, eggs, red meat, fish oil, cheese, beans, peas, and soy. Male albino rats were divided into sham, control, 10-mg/kg bwt L-lysine, and 20-mg/kg bwt L-lysine groups. At the end of treatment, we determined the levels of oxidative and inflammatory markers, myeloperoxidase (MPO) and catalase activities, total cell count, the wet/dry ratio of lung tissue, and total protein content. Furthermore, the effect of L-lysine on the cellular architecture of lung tissue was evaluated. L-Lysine significantly reduced the magnitude of lipid peroxidation; total protein content; wet/dry ratio of lung tissue; tumor necrosis factor-alpha, interleukin-8, and macrophage inhibitory factor levels; MPO activity; and total cell, neutrophil, and lymphocyte counts, and it increased the reduced glutathione levels and the glutathione peroxidase, superoxide dismutase, and catalase activities. A normal cellular architecture was noted in rats in the sham group, whereas proinflammatory changes, such as edema and neutrophilic infiltration, were detected in rats in the control group. L-lysine significantly ameliorated these proinflammatory changes. Thus, L-lysine has the potential for the treatment of sepsis-induced CLI.


Assuntos
Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/etiologia , Lisina/uso terapêutico , Substâncias Protetoras/uso terapêutico , Sepse/complicações , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Contagem de Células , Doença Crônica , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Mediadores da Inflamação/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Lesão Pulmonar/patologia , Lisina/farmacologia , Masculino , Peroxidase/metabolismo , Substâncias Protetoras/farmacologia , Ratos , Sepse/patologia , Superóxido Dismutase/metabolismo
18.
Medicina (Kaunas) ; 55(5)2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31121838

RESUMO

Background and objectives: Ischemia-reperfusion (IR) caused by infrarenal abdominal aorta cross-clamping is an important factor in the development of ischemia-reperfusion injury in various distant organs. Materials and Methods: We investigated potential antioxidant/anti-inflammatory effects of thymosin beta 4 (Tß4) in a rat model of abdominal aortic surgery-induced IR. Tß4 (10 mg/kg, intravenous (i.v.)) was administered to rats with IR (90-min ischemia, 180-min reperfusion) at two different periods. One group received Tß4 1 h before ischemia, and the other received 15 min before the reperfusion period. Results: Results were compared to control and non-Tß4-treated rats with IR. Serum, bronchoalveolar lavage fluid and lung tissue levels of oxidant parameters were higher, while antioxidant levels were lower in the IR group compared to control. IR also increased inflammatory cytokine levels. Tß4 reverted these parameters in both Tß4-treated groups compared to the untreated IR group. Conclusions: Since there is no statistical difference between the prescribed results of both Tß4-treated groups, our study demonstrates that Tß4 reduced lung oxidative stress and inflammation following IR and prevented lung tissue injury regardless of timing of administration.


Assuntos
Lesão Pulmonar/etiologia , Traumatismo por Reperfusão/complicações , Timosina/análise , Análise de Variância , Animais , Aorta Abdominal/anormalidades , Modelos Animais de Doenças , Lesão Pulmonar/sangue , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Fatores de Proteção , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/sangue , Timosina/sangue , Turquia
19.
Undersea Hyperb Med ; 46(2): 153-157, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31051060

RESUMO

In 2018, the Medical Panel of the NATO Underwater Diving Working Group (UDWG) discussed the question of the rescue and management of a submerged unresponsive compressed-gas diver. The Panel reviewed the 2012 recommendation by the UHMS Diving Committee with respect to the specific recommendation in a convulsing diver using a half-face mask and separate mouthpiece, to delay surfacing until the clonic phase had subsided if the mouthpiece was in place. There is a paucity of scientific, epidemiological, experimental and observational human studies to substantiate this guidance. Experimental animal studies suggest that the likelihood of a complete airway obstruction during an ongoing seizure is low and that there is a high likelihood of surviving pulmonary barotrauma caused by complete airway closure. Airway management and control is an essential step in the management of the unresponsive diver and would be challenging to achieve in the underwater environment. Even in the military setting, it will be difficult to provide sufficient training to enable divers to handle such a situation. In this very rare scenario it is considered that emergency guidelines should be clear, concise and easy to follow. The UDWG therefore recommends that all unconscious military divers in this situation should be rescued to surface without waiting for clonic seizures to subside. Training organizations for recreational and occupational divers should consider whether this guidance should be applied for civilian divers as well.


Assuntos
Mergulho/efeitos adversos , Guias de Prática Clínica como Assunto , Trabalho de Resgate/normas , Convulsões , Inconsciência , Barotrauma/complicações , Tomada de Decisões , Fidelidade a Diretrizes , Humanos , Lesão Pulmonar/etiologia , Militares , Trabalho de Resgate/métodos , Convulsões/etiologia , Inconsciência/etiologia
20.
Med Sci Monit ; 25: 3288-3297, 2019 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-31054221

RESUMO

BACKGROUND Cold-inducible RNA-binding protein (CIRP) has been identified as an inflammatory mediator that exerts its function in inflammatory diseases. However, the roles of CIRP in patients who received cardiovascular surgery necessitating cardiopulmonary bypass (CPB) are still unknown. The aim of this study was to examine CIRP levels and attempt to evaluate whether CIRP could serve as a predictor for lung dysfunction after cardiovascular surgery. MATERIAL AND METHODS Plasma CIRP levels were detected by ELISA in 31 patients who received cardiovascular surgery at different time points. Selective inflammatory cytokines (TNF-alpha, IL-6, IL-10, and TLR4) and mediators (Ang II, PAI-1, and soluble E-selectin) were also detected. Selective laboratory and clinical parameters were recorded at scheduled time points. RESULTS Compared with pre-operation levels, CIRP levels significantly increased 6 h after cardiovascular surgery with CPB. Multiple linear regression analysis showed that the length of CPB time contributed to CIRP production (P=0.013). Furthermore, CIRP was associated with Ang II (r=0.438, P=0.016), PAI-1 (r=0.485, P=0.006), and soluble E-selectin (r=0.470, P=0.008), which partly reflected lung injuries. Multiple linear regression analysis showed that CIRP levels were independently associated with PaO2/FiO2 ratios (P=0.021). CONCLUSIONS The length of CPB time contributed to the upregulation of CIRP in patients who received cardiovascular surgery with CPB. CIRP levels could serve as a biomarker to predict the onset of lung injury induced by cardiovascular surgery.


Assuntos
Ponte Cardiopulmonar/métodos , Procedimentos Cirúrgicos Cardiovasculares/métodos , Lesão Pulmonar/sangue , Proteínas de Ligação a RNA/sangue , Biomarcadores/sangue , Procedimentos Cirúrgicos Cardiovasculares/efeitos adversos , Citocinas/sangue , Feminino , Humanos , Lesão Pulmonar/etiologia , Lesão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Testes de Função Respiratória
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