The telomerase activator TA-65 protects from cigarette smoke-induced small airway remodeling in mice through extra-telomeric effects.

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.

[Halitosis: multidisciplinary diagnostic and therapeutic approaches]. / Halitose: approches diagnostiques et thérapeutiques pluridisciplinaires.

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.

Pulse wave velocity is lower in trained than in untrained sickle cell trait carriers.

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 (n = 10), untrained SCT carriers (n = 23) and trained SCT carriers (n = 17) who reported at least 10 hours of physical exercise per week. RESULTS: Untrained SCT carriers had higher pulse wave velocity (p = 0.032) and blood viscosity (p < 0.001) than their trained counterparts. In addition, untrained SCT carriers had higher blood viscosity (p < 0.001) 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.