Quantitative Changes in the Sleep EEG at Moderate Altitude (1630 m and 2590 m)

Background

Previous studies have observed an altitude-dependent increase in central apneas and a shift towards lighter sleep at altitudes >4000 m. Whether altitude-dependent changes in the sleep EEG are also prevalent at moderate altitudes of 1600 m and 2600 m remains largely unknown. Furthermore, the relationship between sleep EEG variables and central apneas and oxygen saturation are of great interest to understand the impact of hypoxia at moderate altitude on sleep.

Methods

Fourty-four healthy men (mean age 25.0±5.5 years) underwent polysomnographic recordings during a baseline night at 490 m and four consecutive nights at 1630 m and 2590 m (two nights each) in a randomized cross-over design.

Results

Comparison of sleep EEG power density spectra of frontal (F3A2) and central (C3A2) derivations at altitudes compared to baseline revealed that slow-wave activity (SWA, 0.8–4.6 Hz) in non-REM sleep was reduced in an altitude-dependent manner (∼4% at 1630 m and 15% at 2590 m), while theta activity (4.6–8 Hz) was reduced only at the highest altitude (10% at 2590 m). In addition, spindle peak height and frequency showed a modest increase in the second night at 2590 m. SWA and theta activity were also reduced in REM sleep. Correlations between spectral power and central apnea/hypopnea index (AHI), oxygen desaturation index (ODI), and oxygen saturation revealed that distinct frequency bands were correlated with oxygen saturation (6.4–8 Hz and 13–14.4 Hz) and breathing variables (AHI, ODI; 0.8–4.6 Hz).

Conclusions

The correlation between SWA and AHI/ODI suggests that respiratory disturbances contribute to the reduction in SWA at altitude. Since SWA is a marker of sleep homeostasis, this might be indicative of an inability to efficiently dissipate sleep pressure.     

Is carbon dioxide (CO2) a useful short acting anaesthetic for small laboratory animals?

The anaesthetic effect of carbon dioxide (CO2) was investigated under predetermined exposure times in rats, mice and guinea pigs with admixture of 20% of oxygen (O2), and with 20% of ambient air in rats. In rats first symptoms (median) were detectable between 7 and 9.5 s, the induction time (median) varied between 16 and 20.5 s and the surgical tolerance (median) was 40 s (after 60 s of exposure) and 53.5 s (after 120 s of exposure) to 80% CO2/20% O2. When O2 was replaced by ambient air, a surgical tolerance of 53.5 s (after 60 s of exposure) and 77 s (after 120 s of exposure) was measured. In mice the induction time to 80% CO2/20% O2 was 10 s and the surgical tolerance 19.5 s (after 120 s of exposure). Guinea pigs showed an induction period of 20 s and a surgical tolerance of 50 s (after 30 s of exposure) to 80% CO2/O2. Recovery was short and smooth in all species. This method of general anaesthesia seems to be suitable for short and painful interventions, mainly in rats, but also in guinea pigs.     

Optimization of the Interferon Assay Using Inhibition of Semliki Forest Virus-Ribonucleic Acid Synthesis

The method for assaying chicken interferon by its inhibition of viral ribonucleic acid (RNA) synthesis was optimized for the chicken embryo fibroblast-Semliki Forest virus (SFV) system, with respect to time, multiplicity of infection, and addition of actinomycin D and (3)H-uridine. Incorporation of (3)H into viral RNA is reproducible, and amounts to 10(4) to 2 x 10(4) counts per min per uninhibited culture per 1 muCi per 6 hr. The assay may be carried out in less than 1 day and is sensitive (0.05 units/ml) and exact (+/-20% of the mean titers on different days); it can be used for purification procedures as well.     

Carbon monoxide dehydrogenase and acetate thiokinase in Methanothrix soehngenii

Abstract In Methanothrix soehngenii acetate is first activated by an acetate thiokinase rather than a phosphotransacetylase. The specific activity of the acetate thiokinase was 5.29 μmol acetate activated min⁻¹ mg⁻¹ protein with a half maximum rate at 0.74 mM acetate and at 0.047 mM CoA. In cell-free extracts a CO-dehydrogenase activity was measured of 3.02 μmol min⁻¹ mg⁻¹ protein with a half maximum rate at 0.44 mM CO and at 0.18 mM methylviologen. NADP and NAD could not replace methylviologen. F₄₂₀ showed only low activity as electron acceptor.     

4-Anilino-3-cyanobenzo[g]quinolines as kinase inhibitors

A series of 4-anilino-3-cyanobenzo[g]quinolines was prepared as potent kinase inhibitors. Compared with their bicyclic 4-anilino-3-cyanoquinoline analogues, the tricyclic 4-anilino-3-cyanobenzo[g]quinolines are less active against EGF-R kinase, equally active against MAPK kinase (MEK), and more active against Src kinase. For Src kinase inhibition, the best activity is obtained when both the 7- and 8-positions are substituted with alkoxy groups. Several of these kinase inhibitors show potent growth inhibitory activity in tumor cells.     

Analysis of the idiotypic network in tumor immunity

Herein we have analyzed the expression of idiotopes associated with a monoclonal anti-tumor-associated antigen (TAA) antibody in DBA/2 mice which have progressively growing tumors or resist tumor growth. A panel of eight monoclonal antiidiotypic antibodies raised against a monoclonal antibody which reacts with a mouse mammary tumor virus cross-reactive qp52 envelope protein (TAA) of the L1210/GZL lymphoma was used to measure the expression of idiotopes in sera from different treatment groups. Significant correlations between the expression of certain idiotopes and the growth of the tumor or the establishment of anti-tumor immunity are seen. 1) Idiotypes detected by anti-idiotype D11 are high in anti-idiotype immunized progressor or tumor-susceptible mice and low or absent in regressor mice, i.e., the mice immunized with the protective 2F10 anti-idiotype; 2) the 3A4-detected idiotypes are less frequent or absent in irradiated tumor-immunized regressor mice than in untreated mice challenged with live tumor or progressor mice; 3) no difference in the anti-TAA titers is seen in mice in which the tumor growth is inhibited and in mice in which the tumor grows; 4) no difference in 11C1 idiotype + anti-TAA titer was observed between regressor and progressor mice; and 5) mice with normal or accelerated tumor growth have higher titers of idiotypes detected by a polyclonal anti-idiotype. These findings provide evidence for a regulatory idiotype network induced by the growing L1210/GZL tumor or by anti-idiotypic immunization. The titer of anti-TAA antibody does not correlate with the biology of tumor growth, but certain idiotopes correlate with either progressive or regressive tumor behavior. Therefore, the target of the idiotype regulation is likely to be anti-tumor T effector cells. Effective idiotype therapy of tumors must deal with the complexity of idiotype regulation induced by the tumor itself and is unlikely to be successful if anti-idiotypes are used only as internal mimicry of a TAA.