Acute effects of hypertonic saline inhalation on nitric oxide pulmonary diffusing capacity in healthy adults.

We investigated acute effects of inhalation of hypertonic saline solution (HSS) and oxygen (O2, control exposure) on pulmonary diffusing capacity for nitric oxide (DLNO) and carbon monoxide (DLCO). In a randomized crossover study, 20 healthy, non-smoking subjects were allocated to short-term inhalation of HSS or O2. Spirometry [(forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)] and combined single-breath DLNO-DLCO measurements were performed before and immediately after inhalation of either HSS or O2. Percent changes were presented as median values (interquartile range). After HSS inhalation, DLNO, FEV1 and FVC were decreased by -3.0% (-7.3, 0.5), -3.1% (-4.2, -1.6) and -1.2% (-3.3, 0.6), respectively (all P < 0.05), without significant effect on DLCO. No changes in spirometry and diffusing capacity were observed following O2 inhalation. Acute inhalation of HSS causes a slight decrease in membrane conductance, probably as a result of fluid imbalance at the alveolar surface and interstitial fluid accumulation, both of which could impair gas exchange.

Short-term cardiorespiratory adaptation to high altitude in children compared with adults.

As short-term cardiorespiratory adaptation to high altitude (HA) exposure has not yet been studied in children, we assessed acute mountain sickness (AMS), hypoxic ventilatory response (HVR) at rest and maximal exercise capacity (CPET) at low altitude (LA) and HA in pre-pubertal children and their fathers. Twenty father-child pairs (11 ± 1 years and 44 ± 4 years) were tested at LA (450 m) and HA (3450 m) at days 1, 2, and 3 after fast ascent (HA1/2/3). HVR was measured at rest and CPET was performed on a cycle ergometer. AMS severity was mild to moderate with no differences between generations. HVR was higher in children than adults at LA and increased at HA similarly in both groups. Peak oxygen uptake (VO2 peak) relative to body weight was similar in children and adults at LA and decreased significantly by 20% in both groups at HA; maximal heart rate did not change at HA in children while it decreased by 16% in adults (P < 0.001). Changes in HVR and VO2 peak from LA to HA were correlated among the biological child-father pairs. In conclusion, cardiorespiratory adaptation to altitude seems to be at least partly hereditary. Even though children and their fathers lose similar fractions of aerobic capacity going to high altitude, the mechanisms might be different.

Kinetics of protein import into isolated Xenopus oocyte nuclei.

An in vitro assay for nucleocytoplasmic transport was established in which signal-dependent protein import is reproduced faithfully by isolated purified nuclei. The assay permits the precise quantification of import kinetics and the discrimination between translocation through the nuclear envelope and intranuclear transport. Nuclei were manually isolated from Xenopus oocytes and after manual purification incubated with a medium containing a green fluorescent transport substrate, karyopherins alpha2 and beta1, a red fluorescent control substrate, an energy mix and, for keeping an osmotic balance, 20% (wt/vol) BSA. Import of transport substrates into the nucleus and exclusion of the control substrate were monitored simultaneously by two-color confocal microscopy. Two widely differing import substrates were used: the recombinant protein P4K [480 kDa, four nuclear localization sequences (NLSs) per P4K tetramer], and NLS-BSA (90 kDa, 15 NLSs). The measurements suggested that import, at the specific conditions used in this study, consisted of two consecutive processes: (i) the rapid equilibration of the concentration difference across the nuclear envelope, a process involving binding and translocation of substrate by the nuclear pore complex, and (ii) the dissipation of the intranuclear concentration difference by diffusion.