RESUMEN
Nicotinic α-7 acetylcholine receptor (nAChRα7) is a critical regulator of cholinergic anti-inflammatory actions in several diseases, including acute respiratory distress syndrome (ARDS). Given the potential importance of α7nAChR as a therapeutic target, we evaluated whether PNU-282987, an α7nAChR agonist, is effective in protecting the lung against inflammation. We performed intratracheal instillation of LPS to generate acute lung injury (ALI) in C57BL/6 mice. PNU-282987 treatment, either before or after ALI induction, reduced neutrophil recruitment and IL-1ß, TNF-α, IL-6, keratinocyte chemoattractant (KC), and IL-10 cytokine levels in the bronchoalveolar lavage fluid (P < 0.05). In addition, lung NF-κB phosphorylation decreased, along with collagen fiber deposition and the number of matrix metalloproteinase-9+ and -2+ cells, whereas the number of tissue inhibitor of metalloproteinase-1+ cells increased (P < 0.05). PNU-282987 treatment also reduced lung mRNA levels and the frequency of M1 macrophages, whereas cells expressing the M2-related markers CD206 and IL-10 increased, suggesting changes in the macrophage profile. Finally, PNU-282987 improved lung function in LPS-treated animals. The collective results suggest that PNU-282987, an agonist of α7nAChR, reduces LPS-induced experimental ALI, thus supporting the notion that drugs that act on α7nAChRs should be explored for ARDS treatment in humans.-Pinheiro, N. M., Santana, F. P. R., Almeida, R. R., Guerreiro, M., Martins, M. A., Caperuto, L. C., Câmara, N. O. S., Wensing, L. A., Prado, V. F., Tibério, I. F. L. C., Prado, M. A. M., Prado, C. M. Acute lung injury is reduced by the α7nAChR agonist PNU-282987 through changes in the macrophage profile.
Asunto(s)
Lesión Pulmonar Aguda/prevención & control , Benzamidas/uso terapéutico , Compuestos Bicíclicos con Puentes/uso terapéutico , Lipopolisacáridos/toxicidad , Macrófagos/metabolismo , Receptor Nicotínico de Acetilcolina alfa 7/agonistas , Animales , Líquido del Lavado Bronquioalveolar , Citocinas/genética , Citocinas/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Inflamación/metabolismo , Masculino , Ratones , ARN/genética , ARN/metabolismoRESUMEN
Sakuranetin is the main isolate flavonoid from Baccharis retusa (Asteraceae) leaves and exhibits anti-inflammatory and antioxidative activities. Acute respiratory distress syndrome is an acute failure of the respiratory system for which effective treatment is urgently necessary. This study investigated the preventive and therapeutic effects of sakuranetin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. Animals were treated with intranasal sakuranetin 30 min before or 6 h after instillation of LPS. Twenty-four hours after ALI was induced, lung function, inflammation, macrophages population markers, collagen fiber deposition, the extent of oxidative stress, and the expression of matrix metalloprotease-9 (MMP-9), tissue inhibitor of MMP-9 (TIMP-1) and NF-κB were evaluated. The animals began to show lung alterations 6 h after LPS instillation, and these changes persisted until 24 h after LPS administration. Preventive and therapeutic treatment with sakuranetin reduced the neutrophils in the peripheral blood and in the bronchial alveolar lavage. Sakuranetin treatment also reduced macrophage populations, particularly that of M1-like macrophages. In addition, sakurnaetin treatment reduced keratinocyte-derived chemokines (IL-8 homolog) and NF-κB levels, collagen fiber formation, MMM-9 and TIMP-1-positive cells, and oxidative stress in lung tissues compared with LPS animals treated with vehicle. Finally, sakuranetin treatment also reduced total protein, and the levels of TNF-α and IL-1ß in the lung. This study shows that sakuranetin prevented and reduced pulmonary inflammation induced by LPS. Because sakuranetin modulates oxidative stress, the NF-κB pathway, and lung function, it may constitute a novel therapeutic candidate to prevent and treat ALI.
Asunto(s)
Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/prevención & control , Flavonoides/uso terapéutico , Lesión Pulmonar Aguda/sangre , Lesión Pulmonar Aguda/complicaciones , Animales , Biomarcadores/metabolismo , Polaridad Celular/efectos de los fármacos , Colágeno/metabolismo , Adaptabilidad/efectos de los fármacos , Citocinas/metabolismo , Flavonoides/química , Flavonoides/farmacología , Mediadores de Inflamación/metabolismo , Leucocitos/efectos de los fármacos , Lipopolisacáridos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones Endogámicos BALB C , Modelos Biológicos , Estrés Oxidativo/efectos de los fármacos , Fosforilación/efectos de los fármacos , Neumonía/sangre , Neumonía/complicaciones , Neumonía/tratamiento farmacológico , Neumonía/fisiopatología , Subunidades de Proteína/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factores de Tiempo , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Factor de Transcripción ReIA/metabolismoRESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and inflammation. Natural products, such as monoterpenes, displayed anti-inflammatory and anti-oxidant activities and can be used as a source of new compounds to COPD treatment. Our aim was to evaluate, in an elastase-induced pulmonary emphysema in mice, the effects of and underlying mechanisms of three related natural monoterpenes (p-cymene, carvacrol and thymol) isolated from essential oil from leaves Lippia sidoides Cham. (Verbenaceae). METHODS: Mices received porcine pancreatic elastase (PPE) and were treated with p-cymene, carvacrol, thymol or vehicle 30 min later and again on 7th, 14th and 28th days. Lung inflammatory profile and histological sections were evaluated. RESULTS: In the elastase-instilled animals, the tested monoterpenes reduced alveolar enlargement, macrophages and the levels of IL-1ß, IL-6, IL-8 and IL-17 in bronchoalveolar lavage fluid (BALF), and collagen fibers, MMP-9 and p-65-NF-κB-positive cells in lung parenchyma (p < 0.05). All treatments attenuated levels of 8-iso-PGF2α but only thymol was able to reduced exhaled nitric oxide (p < 0.05). CONCLUSION: Monoterpenes p-cymene, carvacrol and thymol reduced lung emphysema and inflammation in mice. No significant differences among the three monoterpenes treatments were found, suggesting that the presence of hydroxyl group in the molecular structure of thymol and carvacrol do not play a central role in the anti-inflammatory effects.
Asunto(s)
Enfisema/tratamiento farmacológico , Interleucinas/metabolismo , Lippia/química , Monoterpenos/administración & dosificación , Elastasa Pancreática/efectos adversos , Animales , Líquido del Lavado Bronquioalveolar/inmunología , Cimenos , Modelos Animales de Enfermedad , Enfisema/inducido químicamente , Enfisema/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Macrófagos Alveolares/efectos de los fármacos , Ratones , Monoterpenos/química , Monoterpenos/aislamiento & purificación , Monoterpenos/farmacología , Aceites Volátiles/química , Hojas de la Planta/química , Timol/administración & dosificación , Timol/química , Timol/aislamiento & purificación , Timol/farmacologíaRESUMEN
In the past, aesthetics had a secondary role in implant rehabilitation. Nowadays, the search for a perfect and harmonious aesthetic has stimulated the development of new materials and techniques. Due to this aesthetic requirement, the hybrid abutment (titanium link + zirconia) emerged as an alternative to metallic pillars. The hybrid abutment made a more favorable aesthetic possible, provided reliable mechanical properties, and increased biocompatibility to the surrounding tissues. Additionally, the individual zirconia abutment improves the emergency profile and the final white aesthetics. The objective of this paper is to report a clinical case with a manufactured individualized hybrid abutment for a metal-free indirect restoration, showing the applicability, mechanical properties, and biocompatibility of the hybrid abutment.
RESUMEN
Avaliar os conhecimentos adquiridos sobre ergonomia pelos acadêmicos de Odontologia e sua aplicação no atendimento clínico, através de um estudo transversal com abordagem quantitativa. Os dados foram tabulados e analisados estatisticamente no programa Statistical Package for Social Sciences SPSS, pelos testes de qui-quadrado e exato de Fisher, considerando a significância estatística de 5% (p<0,05). A amostra foi constituída de 145 alunos, sendo 72% do sexo feminino, idade média de 23,1 anos. Houve associação estatisticamente significante entre as variáveis: seguir as normas e ter dificuldade para realizá-las (p = 0,021); seguir as normas ergonômicas e posicionar as costas levemente inclinadas (p<0,001); manter os braços apoiados ao tórax (p=0,044). Quanto à prática de alongamento para prevenir lesões não foi observada associação estatisticamente significante. O incômodo em relação ao não cumprimento das normas de ergonomia foi relatado por 72,3% de indivíduos que seguem as normas e por 97,05% que não seguem, observando-se associação estatisticamente significante (p=0,002). O incômodo relatado esteve associado estatisticamente (p<0,05) com o cumprimento das normas de ergonomia (p=0,002), com a dificuldade de seguir as normas de ergonomia (p=0,001) e por considerar a ergonomia fator importante (p=0,031). Também foi estatisticamente significante a associações entre o período cursado e o cumprimento das normas de ergonomia (p=0,011) e entre o período cursado e a presença de incômodo devido à falta de ergonomia (p=0,016). Apesar do relato do conhecimento sobre as normas ergonômicas, muitos não aplicam por dificuldade em segui-las, embora os incômodos sentidos devido ao não cumprimento da ergonomia não foram estatisticamente significantes(AU)
Assess knowledge acquired by dental students and its enforcement in clininal care through a cross sectional study with quantitative approach. Data was statistically analyzed using the Statistical Package for Social Sciences SPSS, by chi-square and Fisher exact tests, considering the statistical significance of 5% (p<0.05). The sample consists 145 students, 72% female, whose mean age is 23.1. There was a statistically significant association between those variables: following the rules and having difficulties in performing them (p=0.021); following ergonomic standards and positioning the back slightly tilted (p<0.001); keeping the arms on the chest (p = 0.044). Statistically significant association was not observed in the practice of stretching in order to prevent injury. Nuisance for not fulfilling the ergonomic standards was reported by 72.3% of the individuals who follow the rules and 97,05% by the ones who don't, with that, detecting statistically significant association (p = 0.002). This discomfort was statistically associated (p<0.05) with compliance of ergonomic standards (p = 0.002), with the difficulty of following the ergonomics standards (p = 0.001) and for considering ergonomics an important factor (p = 0.031). It was also statistically significant associations between coursed term and compliance with ergonomic standards (p = 0.011) and between coursed period and the presence of nuisance due to lack of ergonomics. (p = 0.016). In spite of stating knowledge of ergonomics rules, many do not fulfill them for difficulty, although the specific discomfort for not complying ergonomics was not statistically significant(AU)