RESUMEN
Acute viral respiratory infections are commonly associated with alterations in lung growth. Recently, fractal techniques have been demonstrated to show changes in alveolar perimeter after canine adenovirus type 2 (CAV2) infection in a beagle puppy model. In the present study, we investigated whether the fractal dimension (Df) of the alveolar perimeter was changed in the acute phase (2-3 weeks after inoculation, 131d CAV2 group) or during the recovery phase (approximately 22 weeks after inoculation, 235d CAV2 group) after a single bout of CAV2. There were sham CAV2 groups, 130d and 238d controls, corresponding to the CAV2 groups. The Df of alveolar perimeter length was significantly increased in the 235d CAV2 puppies compared to all of the other beagle puppy groups. On the other hand, the fractal dimensions for alveolar perimeter length for the other beagle puppy groups were very similar. In a related human study of patients (age range of 25 h to 19 y, N = 11), who died of non-respiratory causes, showed no consistent change in Df of alveolar perimeter length with normal lung growth and development. We conclude that fractal analysis of alveolar perimeter length can be used as an index of permanent lung injury after insult to the growing lungs.
Asunto(s)
Infecciones por Adenoviridae/patología , Adenovirus Caninos/fisiología , Alveolos Pulmonares/patología , Enfermedad Aguda , Infecciones por Adenoviridae/fisiopatología , Adolescente , Adulto , Análisis de Varianza , Animales , Autopsia , Niño , Preescolar , Convalecencia , Modelos Animales de Enfermedad , Perros , Femenino , Fractales , Humanos , Procesamiento de Imagen Asistido por Computador , Lactante , Recién Nacido , Masculino , Embarazo , Alveolos Pulmonares/crecimiento & desarrollo , Alveolos Pulmonares/ultraestructura , Alveolos Pulmonares/virologíaRESUMEN
The lazaroid (21-aminosteroid) analogue U75412E was evaluated in rabbits exposed to diesel fuel-polycarbonate plastic smoke. Inhalation of total of 4.6 mg U75412E aerosolized at a rate of 1.53 mg/min for 3 min before or after smoke significantly prevented or limited the extent of alveolar hypoventilation, interstitial edema, and tumor necrosis factor-alpha (TNF-alpha) by pulmonary alveolar macrophages (PAM) ex vivo observed at 2 h. The smoke-induced changes in wet lung/body weight ratios and the production of superoxide (O2-) by PAM ex vivo were also attenuated by the drug treatment after smoke exposure (p < 0.05). This study suggests that lazaroids may ameliorate the oxygen-radical-initiated cytokine processes and inflammation cascade as a result of the smoke insult.
Asunto(s)
Antioxidantes/farmacología , Macrófagos Alveolares/efectos de los fármacos , Lesión por Inhalación de Humo/prevención & control , Esteroides/farmacología , Factor de Necrosis Tumoral alfa/efectos de los fármacos , Análisis de Varianza , Animales , Antioxidantes/administración & dosificación , Bioensayo , Modelos Animales de Enfermedad , Femenino , Pulmón/patología , Necrosis , Intercambio Gaseoso Pulmonar/efectos de los fármacos , Conejos , Esteroides/administración & dosificación , Factor de Necrosis Tumoral alfa/análisisRESUMEN
The effects of the lazaroid analogue U75412E (21-[4-(3-ethylamino-2-pyridinyl)-1-piperazinyl]-16 alpha-methylpregna-1,4,9]-(11)-triene-3,20-dione) were examined in an acute lung injury rabbit model. Standard doses of 0, 8 and 16 mM U75412E were aerosolized and ventilated into the lungs for 3 min. via an endotracheal tube. A 60 tidal volume dose of diesel fuel-polycarbonate plastic smoke was then instilled, followed by mechanical ventilation for one hour. Pretreatment with 16 mM U75412E significantly increased blood PaO2 and pH values, and decreased blood PaCO2 as compared to smoke only exposures. It also significantly decreased the total cell counts and granulocytes in bronchoalveolar lavage fluid, and the ability of pulmonary alveolar macrophages to produce tumour necrosis factor-alpha in vitro after cell isolation and culture. Histopathology indicated that 16 mM U75412E pretreatment attenuated increases in wet lung/body weight ratios, inflammatory focus, and interstitial oedema associated with smoke insult. In summary, U75412E pretreatment may possess the potential to improve acute smoke-induced lung injury, in part, through modulation of tumour necrosis factor-alpha production from pulmonary alveolar macrophages.
Asunto(s)
Antioxidantes/farmacología , Macrófagos Alveolares/efectos de los fármacos , Lesión por Inhalación de Humo/prevención & control , Esteroides/farmacología , Animales , Líquido del Lavado Bronquioalveolar , Dióxido de Carbono/sangre , Recuento de Células , Células Cultivadas , Femenino , Gasolina , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/ultraestructura , Oxígeno/sangre , Cemento de Policarboxilato , Intercambio Gaseoso Pulmonar/efectos de los fármacos , Conejos , Lesión por Inhalación de Humo/patología , Superóxidos/metabolismo , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Through a simulated flightline exposure protocol, Fischer 344 rats (F344) were subjected to an aerosol/vapor mix of the military jet fuel, JP-8. Previous studies with this model of lung injury have revealed significant increases in pulmonary resistance, increased alveolar clearance of 99mTcDTPA, and a decrease in bronchoalveolar lavage fluid (BALF) concentration of the neuropeptide substance P (SP). Exposures to JP-8 were nose-only and for one hour daily. Six groups of Fischer 344 rats were exposed for 7, 28, or 56 days at two JP-8 concentrations (low dose = 469-520 mg/m3/hr, high dose = 814-1263 mg/m3/hr). Exposed groups were matched with longitudinal controls. In response to JP-8 inhalation, exposure animals demonstrated a dose-dependent as well as duration-determined reduction in BALF SP concentration. Both JP-8 concentrations caused significant pathological changes in lower pulmonary structures.