Dynamics of oxidation stress markers during long-term antiorthostatic hypokinesia: A retrospective study

Nine volunteers aged 27 to 42 participated in an experiment with 370-day antiorthostatic hypokinesia at–5°C, and their blood serum samples were tested for the concentrations of lipid peroxidation (LPO) derivatives, including diene conjugates (DCs), malonic dialdehyde (MDA), and Schiff bases (SBs), and indices of the antioxidant defense system, including the tocopherol (TP) concentration and total antioxidant activity (AOA). The subjects were divided into two groups, which differed in physical training regimen and prophylaxis measures. Initial LPO steps were inhibited in both of the groups by 54–73% from day 50, while the level of SBs, which are final LPO products, decreased by 50–61% by day 230 and remained much the same up to the end of the experiment. The MDA and SB concentrations decreased by a factor of 1.6–2.3 during recovery. Total AOA decreased as an aftereffect during recovery to a level far lower than physiologically normal. Based on the significant inhibition of free-radical LPO throughout the experiment, long-term adaptation to simulated hypogravity was accompanied by a pronounced decrease in biological oxidation and caused severe stress. Substantial long-term readaptation stress developed during recovery after 370-day antiorthostatic hypokinesia, as was evident from the facts that the LPO activity was almost halved, TP concentration significantly increased, and the functional reserves of water-soluble antioxidants were exhausted. Lack of LPO activation was assumed to reflect adequate compensation in the subjects.     

Skin electrical activity of the stomach and intestine during long-term antiorthostatic hypokinesia

The skin electrical activity of the gastrointestinal tract in the stomach and small intestine frequency ranges was studied for four months in 13 men under the conditions of antiorthostatic hypokinesia (AOH). On an empty stomach, both the gastric and small intestine electrical activities increased to a level comparable with that of the increase detectable after eating under the conditions of normal motor activity, whereas the response to food stimulation was inhibited. The ratios between the parameters of spectral analysis testified to a higher tonic component in the stomach and a higher peristaltic component in the intestine under the conditions of AOH. The observed changes in the gastric and intestinal electrical activities were observed against a background of a hypersecretory state of the stomach and an increase in the intestinal contents. During the readaptation period, both the gastric and intestinal electrical activities increased significantly, whereas the response to food stimulation was inhibited.     

Long-term antiorthostatic hypokinesia stimulates storage of osmotically inactive sodium in the human body

Changes in the water and sodium balances and in the states of the fluid compartments of the human body observed in experiments performed with healthy subjects exposed to long-term (120 days) antiorthostatic hypokinesia (ANOH) were analyzed. A hypothesis was suggested that the normal dietary consumption of sodium could be associated with the accumulation of osmotically inactive sodium in the body of a healthy person (independently of changes in the total water content). The results agree with the assumption that considerable amounts of osmotically inactive sodium may be stored in the human body. This hypothesis was confirmed by the inversion of the correlation between the cumulative sodium balance and the total water content of the body found both in the group-averaged data and in individual data. This nonsmotic sodium accumulation may take place not only during deviations from its normal consumption, but also during its regular dietary supply. Accumulation of sodium in these stores and its depletion are not associated with any significant changes in the volumes of body fluids. Infradian rhythmic changes in the sodium balance observed in some subjects exposed to the long-term ANOH, which were not caused by any periodic external influences, indicated the existence of a specific mechanism regulating the sodium content of the body. This mechanism must be significantly more inert and less precise than the fast regulation of the volume, osmolality, and ionic composition of extracellular fluids.     

Changes in metabolic processes in humans during a 120-day antiorthostatic hypokinesia

The activities of organ- and tissue-specific diagnostically significant enzymes, including aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transferase, alkaline phosphatase, total and prostatic acid phosphatase, glutamate dehydrogenase, choline esterase, amylase, lactate dehydrogenase, oxybutyrate dehydrogenase, and creatin phosphokinase (muscular and cardiac isoenzymes), as well as the concentrations of total cholesterol and the cholesterol of high- and low-density lipoproteins, the ratios of their concentrations, and the level of triglycerides, were studied during an experiment with 120-day antiorthostatic (?7°) hypokinesia (ANOH) in the blood of six volunteers (men, 21 to 36 years old). In addition, the indices of lipid peroxidation (LPO) and antioxidant activity were determined, including the concentrations of diene conjugates, malonic dialdehyde, Schiff bases and tocopherol, and the total antioxidant activity. It was found that a 120-day ANOH in this experiment did not result in the formation of deep metabolic shifts accompanied by unfavorable changes in organs and tissues. The changes in cholesterol metabolism during hypokinesia were expressed in the redistribution of cholesterol fractions with the dominance of atherogenic forms and a higher risk of atherogenesis. All of the observed metabolic changes were easily reversible and eliminated during the first month of the recovery period. No signs of a higher intensity of free-radical processes were observed during any of the examination periods due to activation of the antioxidant defense system.     

Effects of hindlimb suspension training on the central and regional hemodynamic responses during 24 hours antiorthostatic hypokinesia in the awake rat

To date the hindlimb suspension model utilizing rats has a wide application to simulate weightlessness. In our previous study we have examined the cardiovascular responses in the tail suspension model using the radiolabeled microspheres technique. We have reported increases of cardiac output (CO) and decreases of total peripheral vascular resistance (TPVR) after 24 hours of head-down tilt (HDT). However, there is no comparison of arterial and venous systems parameters with blood flow changes in organs and tissues. Apart from the preliminary HDT training influence on these parameters is unknown. Thus we aimed to evaluate the role of HDT training in central circulation responses, venous tone and regional blood flow.     

Mechanisms of impairment of precise movements during long-term hypokinesia

Antiorthostaic hypokinesia (AOHK) was found to entail a considerable diminishing of the control system's precision abilities. In the first 14-30 days of the AOHK (the 1st stage), variability of interimpike intervals (ISI) was sharply increased as well as the degree of synchronisation of the motor units' (MU) activity; starting from the 30th day (the 2nd stage), a regular diminishing of the ISI occurred and the MU synchronisation disappeared. The data obtained suggest the different nature of the precision disorders during the 1st and the 2nd stages of the AOHK: a reflex responses to support unloading and the atrophic processes in the muscles, respectively.     

Circadian rhythms of the sex steroids of female Papio hamadryas in long-term hypokinesia

Radioimmunoassay was used to study the effect of restricted motor activity on circadian rhythms of blood plasma sexual steroids and cortisol in female Papio hamadryas during different phases of the menstrual cycle. Instact animals manifested clear-cut circadian rhythms of the testosterone and cortisol content during both the phases and those of estradiol and progesterone during the follicular phase of the cycle. Two-week immobilization did not produce any changes in the general pattern of circadian rhythms of cortisol and testosterone but led to a decrease in their mean daily concentrations, with that decrease being more pronounced for testosterone of females immobilized during the luteal phase. The authors established unbalance of sexual steroids with a dramatic fall of the mean daily concentrations of estradiol and progesterone and desynchronism of their circadian rhythms regardless of the cycle phase at the moment of immobilization. The mechanisms responsible for alterations in circadian rhythms of sexual steroids in hypokinetic females are discussed.     

Morphology of skeletal muscles after long-term hypokinesia and laser acupuncture

Hypokinesia (Hk) lasting for 150 days has been modelling on Wistar male rats by means of their holding in special boxes. After decapitation in 10, 20, 50, 100 and 150 days the muscles of their extremities have been studied, using stereological methods. At Hk, especially for 50 days, inhibition of morphogenesis of ultrastructures and development of certain pathological processes are noted in the muscles with their preponderance in red fibers. Laser puncture stimulates formation of the ultrastructures responsible for contraction and energy supply and sharply decreases development of the destructive processes in muscle fiber, thus providing a satisfactory endurance of hypokinesia.     

Reaction of striated fibers of human skeletal muscles to long-term anti-orthostatic hypokinesia

Eight men have been kept under a strict bed rest. The lower end of the bed has been elevated by 6 degrees. During the whole effect of the antiorthostatic hypokinesia (AOH) in biopsy of the skeletal muscle tissue no gross morphological changes and essential changes in relation of the muscle fiber (MF) types have been found. On the 120th day of AOH without application of any physical loading concentration of RNA, protein metabolism, glycogen, activity of the energetic metabolism enzymes, MF size decrease. Both contractile and energetic apparatus suffers essentially. This demonstrates certain atrophic processes in both types of the MF. Physical loading against the background of AOH, on the 120th day, prevents development of the atrophic processes in MF. This is demonstrated as maintenance of certain metabolic level and less pronounced changes of ultrastructure. On the 360th day of the experiment in the group without any loading, an essential atrophy of MF, a noticeable++ decrease in metabolism are observed. In the test group against the background of AOH the changes in the biopsy fibers are less pronounced and not so uniform. Application of physical loadings contributes to the development of certain adaptive reactions; their positive effect to the skeletal muscle fiber morphology depends on the structural background, against which it acts and their intensity. The earlier the load begins to act and the higher its intensity, the more pronounced is the delay in development of profound atrophic changes.     

Dynamics of long-term genomic selection

Background

Simulation and empirical studies of genomic selection (GS) show accuracies sufficient to generate rapid gains in early selection cycles. Beyond those cycles, allele frequency changes, recombination, and inbreeding make analytical prediction of gain impossible. The impacts of GS on long-term gain should be studied prior to its implementation.

Methods

A simulation case-study of this issue was done for barley, an inbred crop. On the basis of marker data on 192 breeding lines from an elite six-row spring barley program, stochastic simulation was used to explore the effects of large or small initial training populations with heritabilities of 0.2 or 0.5, applying GS before or after phenotyping, and applying additional weight on low-frequency favorable marker alleles. Genomic predictions were from ridge regression or a Bayesian analysis.

Results

Assuming that applying GS prior to phenotyping shortened breeding cycle time by 50%, this practice strongly increased early selection gains but also caused the loss of many favorable QTL alleles, leading to loss of genetic variance, loss of GS accuracy, and a low selection plateau. Placing additional weight on low-frequency favorable marker alleles, however, allowed GS to increase their frequency earlier on, causing an initial increase in genetic variance. This dynamic led to higher long-term gain while mitigating losses in short-term gain. Weighted GS also increased the maintenance of marker polymorphism, ensuring that QTL-marker linkage disequilibrium was higher than in unweighted GS.

Conclusions

Losing favorable alleles that are in weak linkage disequilibrium with markers is perhaps inevitable when using GS. Placing additional weight on low-frequency favorable alleles, however, may reduce the rate of loss of such alleles to below that of phenotypic selection. Applying such weights at the beginning of GS implementation is important.     

The effect of long-term bed-rest head-down-tilt hypokinesia on the functional properties of the human neuromuscular apparatus]

An influence of 120-days antiorthostatic (-6 degrees) hypokinesia (ANOH) on the functional properties of human m. triceps surae (TS) was investigated. After ANOH the maximal force and the maximal voluntary contraction of TS decreased on the average by 45.5% and 33.7%, respectively, and the maximal twitch response force--by 36.7% (P < 0.05-0.01). The value of force deficit increased on the average by 60.2% (P < 0.001), while a relative increase of the TS force contraction decreased in response to pair irritation (P < 0.05-0.01) as well as the velocity properties of TS after ANOH (P < 0.05-0.001). The rate of absolute (c.u.) tension development fell significantly in response to electrical nerve irritation and during voluntary contraction, while the force-velocity muscle properties according to relative (%) parameters remained unchanged. The fatiguability index of TS constituted the average 0.61 +/- 0.02 after ANOH as against 0.80 +/- 0.03 prior to it (P < 0.05). It is postulated the alterations of contractile properties of TS are due both to atrophic processes, muscle length change, condition of sarcoplasmic reticulum and to changes in the state of the central nervous system.     

Dietary glycemic load and glycemic index and risk of coronary heart disease and stroke in Dutch men and women: the EPIC-MORGEN study

Background

The associations of glycemic load (GL) and glycemic index (GI) with the risk of cardiovascular diseases (CVD) are not well-established, particularly in men, and may be modified by gender.

Objective

To assess whether high dietary GL and GI increase the risk of CVD in men and women.

Methods

A large prospective cohort study (EPIC-MORGEN) was conducted within the general Dutch population among 8,855 men and 10,753 women, aged 21–64 years at baseline (1993–1997) and free of diabetes and CVD. Dietary intake was assessed with a validated food-frequency questionnaire and GI and GL were calculated using Foster-Powell''s international table of GI. Information on morbidity and mortality was obtained through linkage with national registries. Cox proportional hazards analysis was performed to estimate hazard ratios (HRs) for incident coronary heart disease (CHD) and stroke, while adjusting for age, CVD risk factors, and dietary factors.

Results

During a mean follow-up of 11.9 years, 581 CHD cases and 120 stroke cases occurred among men, and 300 CHD cases and 109 stroke cases occurred among women. In men, GL was associated with an increased CHD risk (adjusted HR per SD increase, 1.17 [95% CI, 1.02–1.35]), while no significant association was found in women (1.09 [0.89–1.33]). GI was not associated with CHD risk in both genders, while it was associated with increased stroke risk in men (1.27 [1.02–1.58]) but not in women (0.96 [0.75–1.22]). Similarly, total carbohydrate intake and starch intake were associated with a higher CHD risk in men (1.23 [1.04–1.46]; and 1.24 [1.07–1.45]), but not in women.

Conclusion

Among men, high GL and GI, and high carbohydrate and starch intake, were associated with increased risk of CVD.     

Muscle electrolyte measurements during and after hypokinesia in determining muscle electrolyte depletion during hypokinesia in the rat

Hypokinesia (diminished movement) induces muscle mineral depletion. However, the mechanism of muscle mineral depletion during hypokinesia (HK) remains unknown. Measuring electrolyte retention and electrolyte values in muscle, plasma, and urine during and after HK, the aim of this study was to discover if HK could depress mineral retention and lead to muscle mineral depletion. Studies were done on 204 13-wk-old male Wistar rats (370–390 g) during 10 d pre-HK period, 98 d HK period, and 15 d post-HK period. Rats were equally divided into two groups: vivarium control rats (VCR) and hypokinetic rats (HKR). All hypokinetic rats were kept for 98 d in small individual cages, which restricted their movements in all directions without hindering food and water intakes. All control rats were housed for 98 d in individual cages under vivarium control conditions. Both groups of rats were pair-fed. During the HK period skeletal muscle sodium (Na), potassium (K), magnesium (Mg), calcium (Ca), and water content and electrolyte retention decreased significantly (p < 0.05), while urinary and plasma electrolyte levels increased significantly (p < 0.05) in HKR compared with their pre-HK values and their respective VCR. During the initial days of the post-HK period, mineral retention increased significantly (p < 0.05), plasma and urinary electrolyte level decreased significantly (p < 0.05), while muscle electrolyte and water content remained significantly (p < 0.05) depressed in HKR compared with VCR. Muscle mineral and water content, electrolyte retention, plasma, and urinary electrolyte values did not change in VCR compared with their pre-HK values. It was concluded that during HK decreased muscle mineral content may suggest muscle mineral depletion, while increased urinary electrolyte loss and muscle mineral depletion may demonstrate reduced mineral retention. Reduced electrolyte excretion and depressed muscle mineral content during post-HK may indicate skeletal muscle mineral depletion during HK. Dissociation between electrolyte retention and muscle mineral depletion may demonstrate the presence of decreased electrolyte retention as the mechanism of muscle electrolyte depletion during prolonged HK.