Alveolar PCO2 and PO2 of high-altitude natives living at sea level

León-Velarde, Fabiola, Manuel Vargas, Carlos Monge-C.,Robert W. Torrance, and Peter A. Robbins. AlveolarPCO₂ andPO₂ of high-altitude natives livingat sea level. J. Appl.Physiol. 81(4): 1605-1609, 1996.Thisstudy was designed to determine whether subjects born at high altitude(HA; 2,000 m or above) who subsequently move to near sea level (SL)develop end-tidal PCO₂(PET_CO2) andPO₂(PET_O2) valuesthat equal those of SL natives living near SL. A total of 108 male HAnatives living near SL were identified by survey of a district in Lima,Peru, and a further 108 male SL natives from the same district wereidentified as control subjects. Of these subjects, satisfactory datafor inclusion in the study were obtained from 93 HA and 82 SL subjects.Mean PET_CO2 and PET_O2 values were 37.7 ± 2.5 (SD) and 104.7 ± 3.2 Torr, respectively, in HA subjects and37.7 ± 2.2 and 104.8 ± 3.0 Torr, respectively, in SL subjects.The average difference between SL natives and HA natives forPET_CO2 was 0.07 Torr(0.64 to 0.78; 95% confidence interval) and forPET_O2 was 0.05 Torr(0.89 to 0.99, 95% confidence interval). The average age andweight of the SL and HA subjects did not differ, but the HA subjectswere shorter and tended to have larger vital capacities, consistentwith their origin at HA. We conclude that thePET_CO2 andPET_O2 near SL of SL nativesand HA natives do not differ.

     

Cytochrome 3A and 2E1 in human liver tissue: Individual variations among normal Japanese subjects

AimsThe metabolism of drugs, xenobiotic compounds, and other endogenous/exogenous substrates generally begins with their oxidation through cytochrome P450 (CYP). The results of recent pharmacogenetic analyses have demonstrated CYP's polymorphisms to be related to individual differences in metabolism, but only a limited number of CYP3A4 and CYP2E1 variant alleles influence enzymatic activities. Therefore, CYP gene expression profiling of both normal and pathological human livers should provide critical information for an evaluation of the biological significance of CYPs.Main methodsIn our present study, we first characterized the individual differences in CYP3A4 and CYP2E1 expression levels among Japanese normal or non-pathological liver tissue obtained from autopsy or surgery using immunohistochemistry and quantitative RT-PCR array of phase I metabolic enzymes with combined laser capture microscopy and qPCR analysis.Key findingsBoth CYP3A4 and CYP2E1 mRNA and proteins were predominantly detected in hepatocytes surrounding central veins in normal liver, but there were marked individual differences in both CYP3A4 and CYP2E1 mRNA and proteins among the 23 Japanese subjects examined. Individual differences in CYP3A and CYP2E1 subtypes were also detected in the livers obtained from monozygotic neonatal Japanese female twins with different survival periods. CYP3A and CYP2E1-positive cells were decreased in number in non-pathological hepatocytes of diseased livers compared to those in disease-free livers from autopsy.SignificanceThe above results suggest that individual differences in CYP3A4 and CYP2E1 exist among normal human liver tissues and in non-pathological hepatocytes between diseased and normal liver, and these differences may be important in evaluating the pharmacodynamics of various substances.     

Supraorbital transcutaneous neurostimulation has sedative effects in healthy subjects

Background

Transcutaneous neurostimulation (TNS) at extracephalic sites is a well known treatment of pain. Thanks to recent technical progress, the Cefaly^® device now also allows supraorbital TNS. During observational clinical studies, several patients reported decreased vigilance or even sleepiness during a session of supraorbital TNS. We decided therefore to explore in more detail the potential sedative effect of supraorbital TNS, using standardized psychophysical tests in healthy volunteers.

Methods

We performed a double-blind cross-over sham-controlled study on 30 healthy subjects. They underwent a series of 4 vigilance tests (Psychomotor Vigilance Task, Critical Flicker Fusion Frequency, Fatigue Visual Numeric Scale, d2 test). Each subject was tested under 4 different experimental conditions: without the neurostimulation device, with sham supraorbital TNS, with low frequency supraorbital TNS and with high frequency supraorbital TNS.

Results

As judged by the results of three tests (Psychomotor Vigilance Task, Critical Flicker Fusion Frequency, Fatigue Visual Numeric Scale) there was a statistically significant (p < 0.001) decrease in vigilance and attention during high frequency TNS, while there were no changes during the other experimental conditions. Similarly, performance on the d2 test was impaired during high frequency TNS, but this change was not statistically significant.

Conclusion

Supraorbital high frequency TNS applied with the Cefaly^® device decreases vigilance in healthy volunteers. Additional studies are needed to determine the duration of this effect, the underlying mechanisms and the possible relation with the stimulation parameters. Meanwhile, this effect opens interesting perspectives for the treatment of hyperarousal states and, possibly, insomnia.

     

Alveolar PCO2 oscillations and ventilation at sea level and at high altitude.

This study examines the potential for a ventilatory drive, independent of mean PCO2, but depending instead on changes in PCO2 that occur during the respiratory cycle. This responsiveness is referred to here as "dynamic ventilatory sensitivity." The normal, spontaneous, respiratory oscillations in alveolar PCO2 have been modified with inspiratory pulses approximating alveolar PCO2 concentrations, both at sea level and at high altitude (5,000 m, 16,400 ft.). All tests were conducted with subjects exercising on a cycle ergometer at 60 W. The pulses last about half the inspiratory duration and are timed to arrive in the alveoli during early or late inspiration. Differences in ventilation, which then occur in the face of similar end-tidal PCO2 values, are taken to result from dynamic ventilatory sensitivity. Highly significant ventilatory responses (early pulse response greater than late) occurred in hypoxia and normoxia at sea level and after more than 4 days at 5,000 m. The response at high altitude was eliminated by normalizing PO2 and was reduced or eliminated with acetazolamide. No response was present soon after arrival (<4 days) at base camp, 5,000 m, on either of two high-altitude expeditions (BMEME, 1994, and Kanchenjunga, 1998). The largest responses at 5,000 m were obtained in subjects returning from very high altitude (7,100-8,848 m). The present study confirms and extends previous investigations that suggest that alveolar PCO2 oscillations provide a feedback signal for respiratory control, independent of changes in mean PCO2, suggesting that natural PCO2 oscillations drive breathing in exercise.     

Fluctuation of the plasma TRH level in normal subjects in a 4-hour observation period

Radioimmunoassayable TRH and TSH were measured in plasma samples taken at 5 min intervals for 4 hr (2100-0200 hr) from 4 normal male subjects. Three subjects showed a TSH surge at 2135 hr, 2455 hr and 0150 hr, respectively. The mean plasma TRH level of the 4 subjects was 10.3-11.7 pg/ml. Plasma TRH showed random fluctuation, which did not coincide with the nocturnal increase in plasma TSH.