Surfactant-associated protein B (SP-B) is critical to the biophysical function of pulmonary surfactant. No information is available on SP-B synthesis and kinetics in humans. We administered a 24-h i.v. infusion of 13 C-valine as metabolic precursor of SP-B to six newborn infants (weight 3.5 Ϯ 0.5 kg; age 12 d, range 1-43 d). Three of the study infants also received i.v. 2 H-palmitate to label surfactant disaturated phosphatidylcholine (DSPC). SP-B and DSPC were isolated from tracheal aspirates, and their respective 13 C and 2 H enrichments were measured by gas chromatography-mass spectrometry. SP-B kinetics was measured successfully in all six infants. SP-B median (range) fractional synthesis rate was 30% per day (20 -78% per day), secretion time was 4.5 h (1-9 h), time to peak was 24 h (12-36 h), and half-life was 21 h (8 -35 h). The ascending part of the SP-B kinetic curve was similar to the DSPC curve, suggesting similar secretion pathways. SP-B half-life seemed to be shorter than DSPC half-life. These results agree with existing animal data. We conclude that the measurement of SP-B kinetics is feasible in vivo in humans by stable isotope technology. Surfactant-associated proteins B and C (SP-B and SP-C, respectively) represent Ͻ5% of surfactant by weight, but they play a pivotal role in maintaining surfactant function (1). Surfactant deficiency is the hallmark of respiratory distress syndrome in preterm infants. In respiratory distress syndrome, there is a reduced amount of phospholipids (2) and of SP-B and SP-C (3). The key role of SP-B became evident in congenital SP-B deficiency, which is characterized by severe respiratory failure leading ultimately to death unless lung transplant is performed (1,4). To date, there are no data on SP-B kinetics in humans, but information is available in adult and newborn animals, in which radioactive labels can be used. These studies showed differences in SP-B clearance and kinetics depending on animal species and postnatal age (5-7).We recently described methods based on stable isotopes to measure surfactant disaturated-phosphatidylcholine (DSPC) kinetics in humans (8,9). The main objective of this study was to demonstrate the feasibility of measuring SP-B kinetics in vivo in newborn infants by means of stable isotopes. (Table 1) who were admitted to the neonatal intensive care unit, Department of Paediatrics, University of Padua. Inclusion criteria were 1) gestational age Ͼ37 wk, 2) respiratory failure requiring endotracheal intubation for an estimated length of at least 48 h, 3) arterial and venous lines placed for clinical monitoring, and 4) written parental consent. Exclusion criteria were congenital chromosomal abnormalities and exogenous surfactant given at Ͻ48 h before study start. The local Ethics Committee approved the study protocol. METHODS SP-B kinetics was studied in six infantsAll patients received a 24-h constant i.v. infusion of 2 mg/kg/h 1-13 C valine (Mass Trace, Woburn, MA), dissolved in normal saline, while they were on a lipid-free i.v. infusion. In ...
The mouse diaphragm muscle fiber was studied using the loose patch clamp technique. The voltage gated sodium currents were evoked by step pulses from a holding potential of about -70 mV. Following the activation of the sodium current, a very large and fast outward current was evoked. The sensitivity of this current to 4-aminopyridine and tetraethylammonium indicates the potassium ion as the possible carrier for the channel. Furthermore, the sensitivity to tetrodotoxin and extracellular sodium demonstrated the sodium dependence of this current.
A196Eur J Hosp Pharm 2013;20(Suppl 1):A1-A238Results A total of 52 patients (84% women) were prescribed aprepitant during the study period. The average age was 49 years (age range: 19-69 years). The following data were collected: diagnosis and stage of disease, chemotherapy scheme, anti-emesis change cycle number, combination with radiotherapy and alcohol intake. 65% of patients had breast cancer followed by non-small lung cancer (5%). 27% and 25% of cancers were in stages IA and IIA respectively. The most common chemotherapy scheme (55%) for which the change of antiemetic therapy was seen, was FEC 500-100-500. 26% of patients started ondansetron 4 or 8 mg before aprepitant was prescribed. The rest (74%) received aprepitant directly after failing the first line antiemetic therapy. In 40% of patients the antiemetic regimen was changed to the study drug in cycle 2 and in 25% in cycle 3, demonstrating that aprepitant is not used as first-line antiemetic. Only 5 patients received radiotherapy combined with chemotherapy and only in 4 was alcohol intake recorded. Conclusions In our hospital aprepitant is mainly used in chemotherapy regimens that include anthracyclines in combination with cyclophosphamide. It is prescribed after first line antiemetic regimen failure; meeting the indications established by Drug and Therapeutics Committee. However, it would be advisable to cheque the antiemetic guidelines periodically for compliance with reference guides such as NCCN, ASCO, MASCC etc.No conflict of interest.
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