Resveratrol ameliorates DNA damage, prooxidant and antioxidant imbalance in 1,2-dimethylhydrazine induced rat colon carcinogenesis.

Colorectal cancer is one of the most common internal malignancies in Western society. Currently oxidative stress has been increasingly postulated as a major contributor to carcinogenesis. The assessment of damage in various biological matrices, such as tissues and cells, is vital to understand the development of carcinogenesis and subsequently devising intervention strategies. Thus, the major objective of the present study was to examine the effect of resveratrol (Res) on DNA damage in a short-term study of 16 days and circulatory lipid peroxidation, enzymic/non-enzymic antioxidants status in a long-term study of 30 weeks in 1,2-dimethylhydrazine (DMH) induced colon carcinogenesis. Wistar male rats were divided into 6 groups, group 1 were control rats, group 2 rats received Res (8mg/kg body weight, orally, everyday), rats in groups 3-6 were administered (DMH, 20mg/kg body weight, s.c.) as four injections in order to induce DNA damage in the short-term or once a week for the first 15 weeks in the long-term study. In addition to DMH, group 4 (initiation), 5 (post-initiation) and 6 (entire-period) received Res (8mg/kg body weight, p.o., everyday). The results revealed that, supplementation with Res (entire-period) treatment regimen significantly reduced the DMH-induced leukocytic DNA damage (tail length, tail moment, % DNA in the comet tail and olive tail moment) as compared to DMH-alone treated rats. In addition, entire-period Res supplementation increased the enzymic (superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase and glutathione S-transferase) and non-enzymic (reduced glutathione, vitamin C, vitamin E and beta-carotene) antioxidant status with a corresponding decrease in the extent of lipid peroxidation markers (thiobarbituric acid reactive substances, diene conjugates and lipid hydroperoxides). Conversely, Res supplementation during initiation and post-initiation regimen did not produce greater modulatory effects. Our results indicate that DMH-induced DNA damage and oxidative stress were suppressed/prevented effectively by chronic Res supplementation.

Association of prematurity, lung disease and body size with lung volume and ventilation inhomogeneity in unsedated neonates: a multicentre study.

BACKGROUND: Previous studies have suggested that preterm birth with or without subsequent chronic lung disease is associated with reduced functional residual capacity (FRC) and increased ventilation inhomogeneity in the neonatal period. We aimed to establish whether such findings are associated with the degree of prematurity, neonatal respiratory illness and disproportionate somatic growth. METHODS: Multiple breath washout measurements using an ultrasonic flowmeter were obtained from 219 infants on 306 test occasions during the first few months of life, at three neonatal units in the UK and Australia. Tests were performed during unsedated sleep in clinically stable infants (assigned to four exclusive diagnostic categories: term controls, preterm controls, respiratory distress syndrome and chronic lung disease). The determinants of neonatal lung function were assessed using multivariable, multilevel modelling. RESULTS: After adjustment for age and body proportions, the factors gestation, intrauterine growth restriction and days of supplemental oxygen were all significantly associated with a reduced FRC. In contrast, increased ventilation inhomogeneity (elevated lung clearance index) was only significantly associated with duration of supplemental oxygen. After adjusting for continuous variables, diagnostic category made no further contribution to the models. Despite using identical techniques, unexpected inter-centre differences occurred, associated with the equipment used; these did not alter the negative association of preterm delivery and disease severity with lung function outcomes. CONCLUSION: Reduction in FRC is independently associated with prematurity, intrauterine growth restriction and severity of neonatal lung disease. Determinants of lung function shortly after birth are highly complex in different disease groups.

Nasal versus face mask for multiple-breath washout technique in preterm infants.

The large dead space associated with face masks might impede the accuracy and feasibility of multiple-breath washout (MBW) measurements in small infants. We asked if a low dead space nasal mask would provide measurements of resting lung volume and ventilation inhomogeneity comparable to those obtained with a face mask, when using the MBW technique. Unsedated preterm infants breathing without mechanical assistance and weighing between 1.50 and 2.49 kg were studied. Paired MBW tests with nasal and face masks were obtained using sulphur hexafluoride (SF(6)) as the tracer gas. The order of mask application was quasi-randomized. Bland-Altman method and intraclass correlation coefficient were used to analyze outcomes. Measurements were obtained in 20 infants with a mean (SD) postmenstrual age of 36 (1.4) w and a test weight of 2.0 (0.3) kg. The mean difference (95% CI) for nasal vs. face mask was -3.2 breaths/min (-6.2, -0.1 breaths/min) for respiratory rate, -1.0 ml/kg (-2.3, 0.3 ml/kg) for lung volume, 0.6 (0.1, 1.1) for lung clearance index, 0.2 (0.1, 0.3) for first to zeroeth moment ratio and 1.33 (0.6, 2.4) for second to zeroeth moment ratio. Paired measurements of lung volume showed acceptable agreement and good correlation, but there was poor agreement and poor correlation between indices of ventilation inhomogeneity obtained with the two masks. Functional dead space of the nasal mask was similar to that of the face mask despite its smaller water displacement volume. During MBW in infants below 2.5 kg body weight, a nasal mask results in comparable lung volume measurements. Indices of ventilation inhomogeneity may not be directly comparable using masks with different dead space.