Effect of doxofylline on pulmonary inflammatory response induced by mechanical ventilation in rats with chronic obstructive pulmonary disease / 中华麻醉学杂志

Objective To evaluate the effect of doxofylline on pulmonary inflammatory response induced by mechanical ventilation in rats with chronic obstructive pulmonary disease (COPD).Methods Thirty adult male Sprague-Dawley rats,aged 8 weeks,weighing 200-250 g,were divided into 3 groups (n=10 each) using a random number table method:control group (C group),COPD group and doxofylline group (Dox group).Rats were fed in normoxia for 2 months,and normal saline 0.2 ml was injected into the trachea on 1st and 30th days in C group.Rats were exposed to cigarette smoke for 30 min every day,lasting for 2 months,and lipopolysaccharide 200 μg (0.2 ml) was injected into the trachea on 1st and 30th days in COPD and Dox groups.Two months later,rats in each group were anesthetized,tracheally intubated,and then mechanically ventilated.Doxofylline 50 mg/kg was intravenously injected immediately after intubation in Dox group,and the equal volume of normal saline was given instead in C and COPD groups.Pulmonary specimens were taken after 120 min of mechanical ventilation for examination of pathological changes and for determination of wet/dry weight ratio (W/D ratio) and tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10) contents (by enzyme-linked immunosorbent assay).Results No significant pathological change of lung tissues was found in C group,and COPD pathological changes were observed in COPD and Dox groups.Compared with C group,the W/D ratio and TNF-α level were significantly increased,and the IL-10 level was decreased in COPD and Dox groups (P＜0.05).Compared with COPD group,the W/D ratio and TNF-α level were significantly decreased,and the IL-10 level was increased in Dox group (P＜0.05).Conclusion Doxofylline can reduce the pulmonary inflammatory response induced by mechanical ventilation in rats with COPD.

Mechanisms involved in anti-aging effects of guarana (Paullinia cupana) in Caenorhabditis elegans

Guarana (Paullinia cupana) is habitually ingested by people in the Amazon region and is a key ingredient in various energy drinks consumed worldwide. Extension in longevity and low prevalence of chronic age-related diseases have been associated to habitual intake of guarana. Anti-aging potential of guarana was also demonstrated in Caenorhabditis elegans; however, the mechanisms involved in its effects are not clear. Herein, we investigated the putative pathways that regulate the effects of guarana ethanolic extract (GEE) on lifespan using C. elegans. The major known longevity pathways were analyzed through mutant worms and RT-qPCR assay (DAF-2, DAF-16, SKN-1, SIR-2.1, HSF-1). The possible involvement of purinergic signaling was also investigated. This study demonstrated that GEE acts through antioxidant activity, DAF-16, HSF-1, and SKN-1 pathways, and human adenosine receptor ortholog (ADOR-1) to extend lifespan. GEE also downregulated skn-1, daf-16, sir-2.1 and hsp-16.2 in 9-day-old C. elegans, which might reflect less need to activate these protective genes due to direct antioxidant effects. Our results contribute to the comprehension of guarana effects in vivo, which might be helpful to prevent or treat aging-associated disorders, and also suggest purinergic signaling as a plausible therapeutic target for longevity studies.

Efeito da teofilina associada ao beta2-agonista inalatório de curta ou longa duração, em pacientes com doença pulmonar obstrutiva crônica estável: revisão sistemática / Effect of theophylline associated with short-acting or long-acting inhaled beta2-agonists in patients with stable chronic obstructive pulmonary disease: a systematic review

OBJETIVOS: Avaliar se o tratamento com teofilina associada ao beta2-agonista inalatório de curta ou longa duração é mais eficaz que o placebo e que o uso isolado de cada um dos fármacos, para os pacientes com doença pulmonar obstrutiva crônica estável. MÉTODOS: Realizou-se uma revisão sistemática com metanálise, sendo selecionados todos os ensaios clínicos aleatórios e duplo-cegos encontrados na literatura. RESULTADOS: Foram incluídos oito estudos. Teofilina associada ao beta2-agonista vs. placebo: houve melhora estatisticamente significante para o VEF1 (L), com média 0,27 (IC95 por cento 0,11 a 0,43); e para a dispnéia, com média -0,78 (IC95 por cento -1,26 a -0,29). Teofilina associada ao beta2-agonista vs. beta2-agonista isolado: nenhuma das metanálises realizadas detectou diferença entre os grupos. Teofilina associada ao beta2-agonista vs. teofilina isolada: houve melhora estatisticamente significante para a dispnéia, com média -0,19 (IC95 por cento -0,34 a -0,04). CONCLUSÕES: Em pacientes com doença pulmonar obstrutiva crônica estável: 1) teofilina associada ao beta2-agonista é mais eficaz que o placebo, em relação ao VEF1 e dispnéia; 2a) teofilina associada ao beta2-agonista é mais eficaz que a teofilina isolada, em relação à dispnéia; e 2b) teofilina associada ao beta2-agonista não é mais eficaz que o beta2-agonista isolado, para quaisquer das variáveis estudadas.

OBJECTIVES: To determine whether, in stable patients with chronic obstructive pulmonary disease, administration of theophylline in combination with short-acting or long-acting inhaled beta2-agonists is more efficacious than is a placebo or each of these drugs used in isolation. METHODS: A systematic review and meta-analysis were carried out. All randomized and double-blind clinical trials found in the literature were selected. RESULTS: A total of eight studies were included. In comparing the effect of theophylline combined with beta2-agonists to that of a placebo, we found a statistically significant improvement in mean FEV1 (0.27 L; 95 percentCI: 0.11 to 0.43) and mean dyspnea (-0.78; 95 percentCI: -1.26 to -0.29). None of the meta-analyses performed detected any difference between the results obtained using theophylline combined with beta2-agonists and those obtained using beta2-agonists alone. When the administration of theophylline combined with beta2-agonists was compared to that of theophylline alone, there was a statistically significant improvement in mean dyspnea (-0.19; 95 percentCI: -0.34 to 0.04). CONCLUSION: In patients with stable chronic obstructive pulmonary disease, theophylline combined with beta2 agonists is more efficacious than is a placebo in terms of improving FEV1 and dyspnea. In addition, theophylline combined with beta2 agonists is more efficacious than is theophylline in improving dyspnea. Furthermore, administration of theophylline combined with beta2 agonists is no more efficacious, for any of the variables studied, than is the use of beta2-agonists in isolation.

Determination of Malondialdehyde Level and XanthineOxidase and Antioxidases Activity inScalding-injured Rats / 第三军医大学学报

The back of rats was immersed in 95℃ water for 10 seconds to produce 10% and 30% TBSA full thickness burn injury. Malondialdehyde (MDA) level in plasma, erythrocytes, the liver and the lungs, the activity of superoxide dismutase (SOD), glutathione peroxidase (GSSG-Px), and catalase (CAT) in the blood, liver and lungs, and the activity of liver xanthine oxidase (XO) were determined 4 hours postburn. It was found that MDA level and SOD activity in rat tissues, XO and CAT activity in the liver, and GSSG-Px activity in the lungs and blood increased significantly aftfe injury. The severity of these changes positively correlated with the area of scalding except the SOD activity in the liver and lungs which showed no significant difference in those animals with 10% and 30% TBSA scalding. However the CAT activity in the blood and lungs decreased postburn and the liver GSSG-Px activity in 10% and 30%TBSA scalding-injured rats was higher and lower than that of the control respectively.The results imply that when scalding involves less area of body surface, the function of anti-peroxidation system of the body will be enhanced by inducing the synthesis of antioxidases; when severe scalding covers larger body surface, the induction of enzyme synthesis will be deficient in some tissues of the body.