Early and Late Postnatal Myocardial and Vascular Changes in a Protein Restriction Rat Model of Intrauterine Growth Restriction

Intrauterine growth restriction (IUGR) is a risk factor for cardiovascular disease in later life. Early structural and functional changes in the cardiovascular system after IUGR may contribute to its pathogenesis. We tested the hypothesis that IUGR leads to primary myocardial and vascular alterations before the onset of hypertension. A rat IUGR model of maternal protein restriction during gestation was used. Dams were fed low protein (LP; casein 8.4%) or isocaloric normal protein diet (NP; casein 17.2%). The offspring was reduced to six males per litter. Immunohistochemical and real-time PCR analyses were performed in myocardial and vascular tissue of neonates and animals at day 70 of life. In the aortas of newborn IUGR rats expression of connective tissue growth factor (CTGF) was induced 3.2-fold. At day 70 of life, the expression of collagen I was increased 5.6-fold in aortas of IUGR rats. In the hearts of neonate IUGR rats, cell proliferation was more prominent compared to controls. At day 70 the expression of osteopontin was induced 7.2-fold. A 3- to 7-fold increase in the expression of the profibrotic cytokines TGF-β and CTGF as well as of microfibrillar matrix molecules was observed. The myocardial expression and deposition of collagens was more prominent in IUGR animals compared to controls at day 70. In the low-protein diet model, IUGR leads to changes in the expression patterns of profibrotic genes and discrete structural abnormalities of vessels and hearts in adolescence, but, with the exception of CTGF, not as early as at the time of birth. Invasive and non-invasive blood pressure measurements confirmed that IUGR rats were normotensive at the time point investigated and that the changes observed occurred independently of an increased blood pressure. Hence, altered matrix composition of the vascular wall and the myocardium may predispose IUGR animals to cardiovascular disease later in life

Complex systems and the technology of variability analysis

Characteristic patterns of variation over time, namely rhythms, represent a defining feature of complex systems, one that is synonymous with life. Despite the intrinsic dynamic, interdependent and nonlinear relationships of their parts, complex biological systems exhibit robust systemic stability. Applied to critical care, it is the systemic properties of the host response to a physiological insult that manifest as health or illness and determine outcome in our patients. Variability analysis provides a novel technology with which to evaluate the overall properties of a complex system. This review highlights the means by which we scientifically measure variation, including analyses of overall variation (time domain analysis, frequency distribution, spectral power), frequency contribution (spectral analysis), scale invariant (fractal) behaviour (detrended fluctuation and power law analysis) and regularity (approximate and multiscale entropy). Each technique is presented with a definition, interpretation, clinical application, advantages, limitations and summary of its calculation. The ubiquitous association between altered variability and illness is highlighted, followed by an analysis of how variability analysis may significantly improve prognostication of severity of illness and guide therapeutic intervention in critically ill patients

Termoplastia brônquica: relato do primeiro tratamento endoscópico de asma na América Latina Bronchial thermoplasty: report on the first endoscopic treatment for asthma in Latin America

A termoplastia brônquica é um novo procedimento broncoscópico que libera energia por radiofreqüência nas vias aéreas, com potencial redução da broncoconstrição causada pela contratura da musculatura lisa. Relatamos o caso de um homem de 48 anos, portador de asma persistente moderada, submetido à termoplastia brônquica. O tratamento aumentou o volume expiratório forçado no primeiro segundo, aumentou o número de dias livres de sintomas, reduziu o uso da medicação de resgate e melhorou o escore no questionário de Juniper Asthma Quality of Life Scale. A termoplastia brônquica foi bem tolerada e segura. Esta foi a primeira termoplastia brônquica na América Latina, com resultados estimulantes após 12 meses quanto ao seu potencial benefício em asmáticos pouco controlados.<br>Bronchial thermoplasty is a new bronchoscopic procedure that delivers radiofrequency energy to the airway and potentially reduces the smooth muscle-mediated bronchoconstriction. We report the case of a 48-year-old man with persistent moderate asthma submitted to bronchial thermoplasty. The treatment increased the forced expiratory volume in one second, increased the number of symptom-free days, reduced the use of relief medications, and improved the Juniper Asthma Quality of Life Scale score. In this patient, bronchial thermoplasty was well tolerated and safe. This was the first bronchial thermoplasty performed in Latin America. At 12 months after the procedure, the results were encouraging in terms of its potential benefits in patients with difficult-to-control asthma

Effect of dexamethasone treatment on serum GH, IGF-I, and the binding proteins IGFBP-1 and-3 in ventilated very preterm infants

Very preterm infants developing bronchopulmonary dysplasia frequently show a compromised growth in the neonatal period especially when steroids are given to facilitate weaning from the ventilator. The aim of this study was to evaluate the short-term effect of dexamethasone (DEXA) on the GH-IGF axis in ventilated very preterm infants developing bronchopulmonary dysplasia. We studied 10 very preterm artificially ventilated infants with bronchopulmonary dysplasia [median (range) gestational age 27.5 wk (25.9-32.0 wk), median (range) birth weight 970 g (610-2150 g)] immediately before and 2 d after the start of DEXA treatment. On both days of study, serum GH profiles were obtained, and serum IGF-I and IGF binding protein (IGFBP) -1 and -3 levels were measured. The ventilation score and the nutritional intake were calculated. Before the start of DEXA treatment, the median serum mean GH level was 12.0 mug/L (6-28.4 mug/L), whereas 2 d after the start of DEXA treatment the median serum mean GH level declined significantly to a value of 4.4 mug/L (1.7-11.9 mug/L). During DEXA treatment, mean, baseline, and maximal GH levels (Pulsar analysis) were significantly lower compared with pretreatment levels (p <0.01, p <0.01, and p <0.05, respectively). Serum IGF-I and IGFBP-3 levels did not decline during DEXA. Serum IGFBP-1 levels were significantly lower compared with pretreatment levels (p <0.01). Serum GH levels during DEXA treatment were correlated with neither the time interval between the administration of DEXA and the second GH profile nor the cumulative DEXA dose administered. Ventilation score and nutritional intake did not significantly correlate with serum GH, IGF-I, or IGFBP-1 or -3 levels, either before or after the start of DEXA. Two days of DEXA treatment in very preterm ventilated infants has a suppressive effect on serum GH levels, without an acute decline in serum IGF-I levels. A concomitant decrease in serum IGFBP-1 levels was found