[Hematopoietic stem cells and immune status of subjects with different hypoxic tolerance].

Intermittent hypoxia treatment (IHT) is gaining attention as a clinical modality due to its capacity to protect cells, tissues, organs, and the whole organism from more intense and/or sustained hypoxia, ischemia and other stresses, to enhance physical and mental capacity. Circulating hematopoietic stem and progenitor cells (HSPC) play an important role in immune response to hypoxia ensuring tissue reparation processes, formation of all types of blood cells etc. There exist considerable individual differences in the capability to mobilize HSPC. This study was designed to compare the effects of IHT on HSPC, various factors of natural resistance and main humoral and cellular components of adaptive immunity in peripheral blood of subjects with normal and reduced tolerance to hypoxic load. Ten healthy male volunteers (age 30,9 +/- 0,6 y.o.) participated in the study and were divided into two groups with reduced (RT, 5 subjects) and normal (NT, 5 subjects) hypoxic tolerance. Criterion for reduced hypoxic tolerance detection was the exceeding deviation of arterial blood pressure, minute ventilation, SaO2 and/or pathological changes in ECG during sustained hypoxia test (breathing with 10% oxygen, 10 min). All subjects were studied before and after a 14 day IHT program consisting of four 5 min bouts/d of breathing 10% O2, with intervening 5 min room air exposures. Immunofluorescence detected HSPCs as CD45+CD34+ cells in peripheral blood. Phagocytic and bactericidal activities of neutrophils, circulating immunoglobulins (IgM, IgG, IgA), immune complexes, complement, and cytokines (EPO, TNF-alpha, IL-4, IFN-gamma) were measured. It was shown that NT subjects had higher hemoglobin and erythrocytes level, hematocrit and physical working capacity, but leukocytes, lymphocytes, CD8+-cells contents and level of IgA were lower than in RT. These differences were preserved after IHT course. CD45+34+cells content was the same in both groups before IHT, but RT subjects demonstrated twice decrease in HSPCs content after IHT as opposed to NT who did not show distinct reactions. A decrease in HSPCs is probably associated with the change of their migration capacity. However, it remains unclear whether there is an inhibition of HSPCs migration into circulation or an activation ofHSPCs escape from circulation. In both cases tissues could accumulate more HSPCs which in turn could enhance hematopoiesis and general regenerative potential. RT group also had lower complement, induced and reserve bactericidal activities of neutrophils which were significantly increased after IHT reaching the level of NT. The level of cytokines EPO, TNF-alpha and IFN-gamma did not differ in both groups before IHT but considerably reduced level of IL-4 was registered in RN patients. IHT sharply lowered pro-inflammatory cytokine TNF-alpha in both groups, significantly increased IL-4 in RT subjects; increasing behavior of IFN-gamma was observed in both groups. EPO was not affected considerably during the study. The findings support the potential for eventual application of IHT for immunotherapy, especially for patients with reduced hypoxic tolerance.

[Insulin resistance and physical performance in middle age and elderly people].

In 43 middle age and elderly people without obesity (body mass index of less than 30 kg/m2) we studied the relationship between insulin resistance (IR) and physical performance. It is shown that in healthy elderly IR is associated with a moderate increase of insulin and a small increase in the level of glucose in the blood plasma. In the middle age people, IR has no effect on physical performance. IR in the elderly people is accompanied by the decrease in physical performance due to less economical for hemodynamic load and oxygen consumption. A lower exercise tolerance in elderly people without obesity can be considered not only as a risk factor for insulin resistance, but also as its consequence.

[Individual characteristics of human adaptation to intermittent hypoxia: possible role of genetic mechanisms].

The majority of the adaptation processes to hypoxia is based on transcriptional regulation by hypoxia-inducible factors--HIFs. Recently the allele polymorphism of oxygen-dependent degradation domain of HIF-lalpha has been described. It consists in the replacement of cytosine for thymine in 1772 location (C1772-->T). The physiological significance of such replacement is obscure. In the investigation of 26 healthy elderly subjects (58.5 +/- 0.7 yr) we tried to verify whether HIF-lalpha polymorphism in exon 12 may identify individual features of adaptation to intermittent hypoxia training (IHT) (isocapnic hypoxic rebreathing technique, 5-min sessions with 5 min rest intervals, 3 times daily during 10 days). The distribution of HIF-l alpha genotypes for C1772-->T were studied by using the polymerase chain reaction and restriction analysis. We detected that all subjects from the group had C/C genotype. Meanwhile, the broad spectrum of adaptive reactions to IHT was observed, from the best adaptation up to disadaptation. IHT enhanced HVRs in the range of 167% - 5%, blood malon dialdehyde content varied from a decrease by 46% up to an increase by 88%, the changes of superoxide dismutase activity varied from +64% to -56% etc. These results suggest that the C1772-->T polymorphism in HIF- 1alpha does not contribute to individual peculiarities of adaptation to IHT. Because the activity of HIF-lalpha is regulated by multiple steps including the transcriptional level, the effect of the polymorphism in enother exons on the adaptive reactions remains to be elucidated.

[Physiological adaptation reactions in patients with ischemic heart disease]. / Zahal'noadaptyvni reaktsiï orhanizmu u khvorykh na ishemichnu khvorobu sertsia.

The condition was studied of bodily general adaptive reactions in patients with different forms of ischemic heart disease (IHD). Unlike healthy subjects, IHD patients displayed predominance of pathogenetic and dysadaptive type reactions. 88 percent of healthy subjects had reactions of sanogenetic character, with 31.1 percent of cases having been found in IHD patients. The spectrum of bodily general adaptive reactions was also distinctive in patients with different forms of IHD.