Pathological aging of the vascular endothelium: are endothelial progenitor cells the sentinels of the cardiovascular system?

Aging is associated with vascular endothelial dysfunction, which ultimately leads to atherosclerosis. On the other hand, it is clear that in young patients with risk factors for cardiovascular diseases (CVD), endothelial dysfunction is an early marker of the ongoing atherogenic process. It is therefore tempting to speculate that risk factors for CVD accelerate the aging process. The aging of an endothelial cell (EC) is not chronological but rather dependent on its replication rate. ECs have a finite number of divisions and enter replicative senescence after exhaustion of this potential. Telomere attrition is believed to be responsible for this phenomenon. Upon reaching a critical minimal telomere length, ECs enter a nondividing state of replicative senescence. Recently, endothelial progenitor cells originating from the bone marrow have been isolated from the circulation. They integrate into the endothelial layer of the vessel and contribute to healing, ischemic repair and angiogenesis. A completely new field of investigation is now open. Are endothelial progenitor cells sensitive to the aging process? Do they prevent endothelial dysfunction? Are they the ultimate shield against the damages induced by risk factors for CVD? There are no definite answers to these questions, but the potential of these cells is tremendous and understanding their physiology is essential.     

Pharmacokinetics of omeprazole in healthy adults and in children with gastroesophageal reflux disease

Studies of the pharmacokinetics of omeprazole in children with gastroesophageal reflux disease (GERD) remain scarce despite the vast number of reports on its efficacy. The objectives of this study were to assess the pharmacokinetics of omeprazole in healthy adults and in children with GERD. Omeprazole (Losec, delayed-release capsules) was administered orally to 18 healthy adults (mean age 36.8 years) and 12 children with GERD (mean age 6.1 years). Blood samples were collected over 5 hours, and plasma concentrations were assessed using liquid chromatography. Population pharmacokinetic parameters were calculated using NONMEM. A 1-compartment model with zero-order absorption and a lag time was used. The population approach was well suited to the limited number of samples available, and residual variability was low. Oral clearance (CL/F) and apparent volume of distribution (V(ss)/F) in healthy adults (Mean +/- SD: 0.62 +/- 0.27 L/h/kg and 0.76 +/- 0.26 L/kg, respectively) were not significantly different than those in children with GERD (0.51 +/- 0.34 L/h/kg and 0.66 +/- 0.25 L/kg, respectively). Healthy adults displayed a statistically significantly longer delay in drug absorption (Lag time: 0.62 +/- 0.15 hours) as compared with that observed in children with GERD (0.12 +/- 0.03 hours, P < 0.05). On the basis of these findings, omeprazole dosings on a milligram-per-kilogram basis are recommended with no further adjustments for the treatment of GERD in children.     

Development of baroreflex control of heart rate in preterm and full term infants

AIM: To study baroreflex maturation by measuring, longitudinally, baroreflex sensitivity in preterm (gestational age 24-37 weeks) and full term infants. METHODS: Baroreflex sensitivity was quantified once a week, one to seven times, by a totally non-invasive method. RESULTS: Baroreflex sensitivity at birth was lower in the preterm infant and increased with gestational age. It also increased with postnatal age, but the values for the preterm infants at term still tended to be lower than the values for full term babies. CONCLUSION: Baroreflex control of heart rate is present in the premature infant, but is underdeveloped and increases with postnatal age. Ex utero maturation seems to be delayed compared with in utero maturation assessed by full term values. These results may reflect sympathovagal imbalance in preterm infants and could identify a population more vulnerable to stress.     

Ultrasonography and videobronchoscopy to assess the subglottic diameter in the paediatric population: a first look

OBJECTIVE: The aim of the study was to evaluate the efficacy of ultrasonography and videobronchoscopy in measuring the subglottic diameter in the paediatric population. DESIGN: A double-blinded, prospective clinical study carried out at the Montreal Children's Hospital, McGill University. METHODS: Children undergoing non-life-threatening bronchoscopy for various reasons had the subglottic diameters measured with ultrasonography, videobronchoscopy, and the traditional method of endotracheal tube sizing during the operative period. Ten patients were enrolled in the study. Parental consent was obtained prior to the procedure. RESULTS: Statistical analysis revealed that although ultrasonography was highly correlated with both videobronchoscopy and endotracheal tube sizing in measuring the subglottic diameter in the paediatric population, the measurements were not accurate in giving an exact value of the diameters in question. Videobronchoscopy was found to highly correlate with endotracheal tube sizing but had values that were slightly larger. CONCLUSION: This study is the first to examine the ability of ultrasonography and videobronchoscopy in evaluating the subglottic diameter in the paediatric population. Videobronchoscopy was shown to correlate highly with the present standard of measurement, namely, endotracheal tube sizing. The difference in measurement between the two was shown to be statistically significant, with videobronchoscopy being the consistently larger of the two. These results are in keeping with the limitations of measurement by the endotracheal tube. Similarly, ultrasonography was also correlated with both videobronchoscopy and endotracheal tube sizing. In contrast, ultrasonography was found to provide measurements that were significantly smaller than the other two methods. This suggests that ultrasonography may be a good technique to follow the change in lesions of the subglottis but may be poor for absolute measurements of this area as it always underestimated the size of the lumen.     

Identification of N,N-disubstituted phenylalanines as a novel class of inhibitors of hepatitis C NS5B polymerase

The HCV NS5B RNA dependent RNA polymerase plays an essential role in viral replication. The discovery of a novel class of inhibitors based on an N,N-disubstituted phenylalanine scaffold and structure-activity relationships studies to improve potency are described.     

The value of the Partogramme in the management of labor.

The Partogramme was evaluated at the University Center for Health Science or Centre Universitaire des Sciences de la Santé (CUSS) in Yaounde, Cameroon, Africa. A retrospective study of 686 patients and a prospective study of 1045 patients were conducted. With the institution of this program, the perinatal mortality decreased by 10 deaths/1000 births. The use of the "alert" and "action" lines offered accurate and reliable guidelines for early detection of abnormal labor. Two-thirds of the morbidity and mortality and 72% of deliveries with medical or surgical interference occurred in the clinical group where the labor curve crossed the action line. Regional values for functional divisions of labor are provided. The advantages of the Partogramme are discussed.