RESUMO
The transcription factor p53 is overexpressed in the lung of patients with emphysema, but it remains unclear if it has a deleterious or protective effect in disease progression. We investigated the role of p53 in the elastase-induced emphysema model and the molecular underlining mechanisms. Wild-type (WT) and p53(-/-) mice were instilled with pancreatic porcine elastase. We quantified emphysema (morphometric analysis), chemokine (C-C motif) ligand 2 (CCL2), and TNF-α in bronchoalveolar lavage (BAL) (ELISA), oxidative stress markers [heme oxygenase 1 (HO1), NAD(P)H dehydrogenase quinone 1 (NQO1), and quantitative RT-PCR], matrix metalloproteinase 12 (MMP12) expression, and macrophage apoptosis (cleaved caspase-3, immunofluorescence). p53 gene expression was up-regulated in the lung of elastase-instilled mice. p53 deletion aggravated elastase-induced emphysema severity, pulmonary inflammation (macrophage and neutrophil numbers and CCL2 and TNF-α levels in BAL), and lung oxidative stress. These findings, except for the increase in CCL2, were reproduced in WT mice transplanted with p53(-/-) bone marrow cells. The increased number of macrophages in p53(-/-) mice was not a consequence of reduced apoptosis or an excess of chemotaxis toward CCL2. Macrophage expression of MMP12 was higher in p53(-/-) mice compared with WT mice after elastase instillation. These findings provide evidence that p53(-/-) mice and WT mice grafted with p53(-/-) bone marrow cells are more prone to developing elastase-induced emphysema, supporting a protective role of p53, and more precisely p53 expressed in macrophages, against emphysema development. The pivotal role played by macrophages in this phenomenon may involve the MMP12-TNF-α pathway.
Assuntos
Pulmão/metabolismo , Macrófagos/metabolismo , Elastase Pancreática , Enfisema Pulmonar/induzido quimicamente , Enfisema Pulmonar/metabolismo , Proteína Supressora de Tumor p53/deficiência , Animais , Apoptose , Transplante de Medula Óssea , Líquido da Lavagem Broncoalveolar/química , Quimiocina CCL2/metabolismo , Modelos Animais de Doenças , Predisposição Genética para Doença , Heme Oxigenase-1/metabolismo , Pulmão/patologia , Macrófagos/patologia , Masculino , Metaloproteinase 12 da Matriz/metabolismo , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , NAD(P)H Desidrogenase (Quinona)/metabolismo , Estresse Oxidativo , Fenótipo , Enfisema Pulmonar/genética , Enfisema Pulmonar/patologia , Enfisema Pulmonar/prevenção & controle , Transdução de Sinais , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismo , Proteína Supressora de Tumor p53/genéticaRESUMO
BACKGROUND: Tobacco consumption is a net increase in our areas. In Senegal, as in other African countries, sponsorship of cultural and sporting events in schools promote tobacco use among schoolchildren. Our objective was to assess the prevalence of tobacco in the French School of Jean Mermoz of Dakar by a survey completed by a measurement of carbon monoxide (CO) in expired air. METHODS: seven hundred forty-one students (n = 402 girls and n = 339 boys), aged 11 to 18 years of French and African cultures, participated in the study. A questionnaire with several items of smoking has been distributed to them . Two weeks after the collection of questionnaires, the CO measuring for all students was conducted. RESULTS: The prevalence of smoking in High School was 23.1% and smoking was found more in boys according to the questionnaire and piCO+TM with 13.7% and 7.1% respectively. It affected over the upper age class or equal to fifteen years. The most mentioned reason for the initiation of smoking (45.4% of smokers) was curiosity with a need to be free, followed by the influence of the environment famial (44.4%) and friendly (20.5%). The measurement of carbon monoxide showed that 12.4% of our subjects had a smoking profile with 8% light smoking, 1% moderate smoking, and severe smoking was 3% of our students. A significant difference (p = 0.0021) between the two prevalences was found. CONCLUSION: The carbon monoxide intoxication by tobacco use is responsible for microcirculatory accidents such as tissue hypoxia, whereas smoking affects young students, in which the phenomenon is more precocious. Thus it is urgent to establish a policy of tobacco control in schools.
Assuntos
Monóxido de Carbono/análise , Fumar/epidemiologia , Adolescente , Distribuição por Idade , Monóxido de Carbono/toxicidade , Criança , Feminino , Humanos , Masculino , Prevalência , Senegal/epidemiologia , Distribuição por Sexo , Prevenção do Hábito de Fumar , Inquéritos e QuestionáriosRESUMO
Small airway remodeling (SAR) is a key phenomenon of airflow obstruction in smokers, leading to chronic obstructive pulmonary disease (COPD). SAR results in an increased thickness of small airway walls, with a combination of peribronchiolar fibrosis with increased fibrous tissue and accumulation of mesenchymal and epithelial cells. SAR pathogenesis is still unclear but recent data suggest that alterations in telomerase activity could represent a possible underlying mechanism of SAR. Our study was dedicated to identify a potential protective role of TA-65, a pharmacological telomerase activator, in a cigarette smoke (CS) model of SAR in mice, and to further precise if extra-telomeric effects of telomerase, involving oxidative stress modulation, could explain it. C57BL/6J mice were daily exposed to air or CS during 4 weeks with or without a concomitant administration of TA-65 starting 7 days before CS exposure. Morphological analyses were performed, and mucus production, myofibroblast differentiation, collagen deposition, as well as transforming growth factor-ß1 (TGF-ß1) expression in the small airway walls were examined. In addition, the effects of TA-65 treatment on TGF-ß expression, fibroblast-to-myofibroblast differentiation, reactive oxygen species (ROS) production and catalase expression and activity were evaluated in primary cultures of pulmonary fibroblasts and/or mouse embryonic fibroblasts in vitro. Exposure to CS during 4 weeks induced SAR in mice, characterized by small airway walls thickening and peribronchiolar fibrosis (increased deposition of collagen, expression of α-SMA in small airway walls), without mucus overproduction. Treatment of mice with TA-65 protected them from CS-induced SAR. This effect was associated with the prevention of CS-induced TGF-ß expression in vivo, the blockade of TGF-ß-induced myofibroblast differentiation, and the reduction of TGF-ß-induced ROS production that correlates with an increase of catalase expression and activity. Our findings demonstrate that telomerase is a critical player of SAR, probably through extra-telomeric anti-oxidant effects, and therefore provide new insights in the understanding and treatment of COPD pathogenesis.
Assuntos
Fumar Cigarros , Doença Pulmonar Obstrutiva Crônica , Telomerase , Camundongos , Animais , Catalase/metabolismo , Telomerase/metabolismo , Remodelação das Vias Aéreas , Fumar Cigarros/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos C57BL , Fibroblastos/metabolismo , Doença Pulmonar Obstrutiva Crônica/etiologia , Colágeno/metabolismo , Fator de Crescimento Transformador beta/metabolismo , FibroseRESUMO
INTRODUCTION: Halitosis is a morbid condition characterized by bad breath. Sometimes it has pathological and social implications. In the context of daily clinical practice, halitosis poses many diagnostic and therapeutic problems. This study aims to investigate the clinical and therapeutic features of this disorder. METHODS: We conducted a cross-sectional study over a one year period. Patients over the age of 15 years presenting with halitosis at the University Hospital Yalgado Ouedraogo were enrolled in the study. Patients with bad breath but presenting with some other problema were excluded. Patient's breath was assessed by a practitioner on the basis of Rosenberg organoleptic test. RESULTS: A total of 35 patients were included, with a sex ratio of 1.2. The average age of patients was 31.9 years. In 57.1% of cases, complaints were made by patients themselves. The mean duration of halitosis was 4.3 years. Nineteen patients had Mel Rosenberg score ≥ 2. Dental caries (07 cases), sinusitis (07 cases), Helicobacter pylori infection (09 cases) and gastrointestinal ulcer (10 cases) were associated with halitosis. Treatment was based on etiology in 82.9% of cases with satisfactory improvement after two weeks in 71.8% of cases. CONCLUSION: Halitosis is a little studied disorder which poses problem in positive diagnosis as well as etiologic problems in our context. The dentist plays a crucial role in identifying the possible cause of halitosis. However, multidisciplinary approach would enable a more effective response.
Assuntos
Cárie Dentária/complicações , Halitose/diagnóstico , Infecções por Helicobacter/complicações , Úlcera Péptica/complicações , Sinusite/complicações , Adolescente , Adulto , Burkina Faso , Estudos Transversais , Cárie Dentária/epidemiologia , Odontólogos/organização & administração , Feminino , Halitose/etiologia , Halitose/terapia , Infecções por Helicobacter/epidemiologia , Humanos , Comunicação Interdisciplinar , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/epidemiologia , Papel Profissional , Sinusite/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Sickle cell trait (SCT) is a benign condition of sickle cell disease. Nevertheless, previous reports showed that SCT carriers have increased blood viscosity and decreased vascular reactivity compared to non-SCT carrier. The benefit of regular exercise on vascular function has been well documented in the general population but no study focused on the SCT population. PURPOSE: The aim of our study was to compare arterial stiffness and blood viscosity between trained and untrained SCT carriers, as well as a group of untrained non-SCT. METHODS: Arterial stiffness (finger-toe pulse wave velocity) and blood viscosity were evaluated in untrained non-SCT carriers (nâ=â10), untrained SCT carriers (nâ=â23) and trained SCT carriers (nâ=â17) who reported at least 10 hours of physical exercise per week. RESULTS: Untrained SCT carriers had higher pulse wave velocity (pâ=â0.032) and blood viscosity (pâ<â0.001) than their trained counterparts. In addition, untrained SCT carriers had higher blood viscosity (pâ<â0.001) than the untrained non-SCT group. A positive association was noted between blood viscosity and pulse wave velocity in the whole study population. CONCLUSION: Our study suggests that regular exercise may be beneficial for the vascular function of SCT carriers.
Assuntos
Viscosidade Sanguínea/fisiologia , Análise de Onda de Pulso/métodos , Traço Falciforme/sangue , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Due to the growing commercial applications of manufactured nanoparticles (NPs), toxicological studies on NPs, especially during the critical window of development, are of major importance. The aim of the study was to assess the impact of respiratory exposure to metallic and metal oxide NPs during pregnancy on lung development of the offspring and to determine the key parameters involved in lung alterations. Pregnant mice were exposed to weekly doses of 100 µg (total dose 300 µg) of titanium dioxide (TiO2), cerium oxide (CeO2), silver (Ag) NPs or saline solution by nonsurgical intratracheal instillation. The offspring lungs were analyzed at different stages of lung development: fetal stage (gestational day 17.5), pulmonary alveolarization (post-delivery day 14.5) and lung maturity (post-delivery day 49.5). Regardless of the type of NP, maternal exposure during gestation induced long-lasting impairment of lung development of the offspring. This effect was accompanied by: i) decreased placental efficiency together with the presence of NPs in placenta, ii) no increase of inflammatory mediators present in amniotic fluid, placenta or offspring lungs and iii) decreased pulmonary expression of vascular endothelial growth factor-α (VEGF-α) and matrix metalloproteinase 9 (MMP-9) at the fetal stage, and fibroblast growth factor-18 (FGF-18) at the alveolarization stage. Respiratory exposure to metallic NPs during pregnancy induces stereotyped impairment of lung development with a lasting effect in adult mice, independently of the chemical nature of the NP.