RESUMO
Despite substantial progress, mortality and morbidity of the acute respiratory distress syndrome (ARDS), a severe form of acute lung injury (ALI), remain unacceptably high. There is no effective treatment for ARDS/ALI. The renin-angiotensin system (RAS) through Angiotensin-converting enzyme (ACE)-generated Angiotensin II contributes to lung injury. ACE2, a recently discovered ACE homologue, acts as a negative regulator of the RAS and counterbalances the function of ACE. We hypothesized that ACE2 prevents Bleomycin (BLM)-induced lung injury. Fourteen to 16-week-old ACE2 knockout mice-male (ACE2(-/y)) and female (ACE2(-/-))-and age-matched wild-type (WT) male mice received intratracheal BLM (1.5U/kg). Male ACE2(-/y) BLM injured mice exhibited poorer exercise capacity, worse lung function and exacerbated lung fibrosis and collagen deposition compared with WT. These changes were associated with increased expression of the profibrotic genes α-smooth muscle actin (α-SMA) and Transforming Growth Factor ß1. Compared with ACE2(-/y) exposed to BLM, ACE2(-/-) exhibited better lung function and architecture and decreased collagen deposition. Treatment with intraperitoneal recombinant human (rh) ACE2 (2 mg/kg) for 21 days improved survival, exercise capacity, and lung function and decreased lung inflammation and fibrosis in male BLM-WT mice. Female BLM WT mice had mild fibrosis and displayed a possible compensatory upregulation of the AT2 receptor. We conclude that ACE2 gene deletion worsens BLM-induced lung injury and more so in males than females. Conversely, ACE2 protects against BLM-induced fibrosis. rhACE2 may have therapeutic potential to attenuate respiratory morbidity in ALI/ARDS.
Assuntos
Bleomicina , Lesão Pulmonar/induzido quimicamente , Pulmão/efeitos dos fármacos , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/farmacologia , Animais , Western Blotting , Ensaio de Imunoadsorção Enzimática , Feminino , Deleção de Genes , Humanos , Masculino , Camundongos , Camundongos KnockoutAssuntos
Filtração , Abastecimento de Água , Adolescente , Adulto , Idoso , Canadá , Carbono , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos de Amostragem , Microbiologia da ÁguaRESUMO
The indicatrices of solar radiation reflected from characteristic natural surfaces were measured with a Nimbus Medium Resolution Radiometer (MRIR) 3 m above the ground. Results indicated that areas such as salt and alkali flats had only small deviations from isotropic reflections, while others such as sparsely vegetated areas had substantial deviations. The indicatrices were strongly dependent on the sun angle; thus a daily variation was found for most features. Typical indicatrices, normalized to nadir angle of zero degrees, are presented along with their impacts on measured albedo, which varies with solar angle. Our results can (1) improve surface albedo considerations using space-generated data, and (2) serve as a more realistic lower boundary condition for atmospheric transfer determinations based on space data.
Assuntos
Secções Congeladas , Microtomia , Métodos , Microscopia , Coloração e Rotulagem , Temperatura , ÁguaRESUMO
Nicotiana glutinosa and pinto bean seedlings (Phaseolus vulgaris) were exposed for short periods (3 days or less) to high concentrations of NO(2) (4.11-20.53 mg/m(3) to compare the resulting leaf lesions with ozone damage produced at concentrations of 0.43 to 0.86 mg/m(3). Although the same physiological age leaf tissue was damaged by both toxicants, damage caused by NO(2) was unlike that caused by ozone. Pinto bean (Phaseolus vulgaris) and Pearson improved tomato (Lycopersicon esculentum) seedlings were continuously exposed for 10 to 22 days, to low concentrations of NO(2) (less than 1.03 mg/m(3)). These exposures caused significant growth suppression, increase in green color (total chlorophyll content), and distortion of leaves.