Changes in Total Cholesterol and Heart Rate in Normotensive and Hypertensive Rats under Combined Influence of Cold Exposure and Hypokinesia.

We studied the effect of hypokinesia alone and in combination with cold exposure on HR and total cholesterol content in the blood serum of Wistar, WKY, and SHR rats. Irrespectively of the season, hypokinesia was associated with a decrease in HR, which is probably a result of reduced body needs due to deceleration of metabolic processes. A significant increase in total cholesterol was found under conditions of cold exposure combined with hypokinesia, which indicates qualitative structural rearrangement of energy metabolism under the influence of environmental factors. In winter, the increase in total cholesterol concentration was more pronounced (by 51.5%) in the group of hypertensive animals. Presumably, the increase in the serum concentration of total cholesterol under conditions of hypokinesia and cold exposure is a predictor of structural changes in the heart.

Peculiarities of Pharmacokinetics and Bioavailability of Some Cardiovascular Drugs under Conditions of Antiorthostatic Hypokinesia.

We studied pharmacokinetics and bioavailability of verapamil, propranolol, and ethacizine in healthy volunteers after single oral administration under normal conditions and on the second day of simulated antiorthostatic hypokinesia modeling some effects of microgravity. Under conditions of antiorthostatic hypokinesia, a tendency to a decrease in half-elimination period, mean retention time, and volume of distribution and an increase in the rate of absorption, ratio of maximum concentrations, and relative rate of absorption of verapamil and propranolol were revealed. For ethacizine, a statistically significant increase in the time of attaining maximum concentration and volume of distribution and a decrease in the maximum concentration, rate of absorption, ratio of maximum concentrations, and relative rate of absorption under conditions of antiorthostatic hypokinesia were found.

Infection as cause of immobility and occurrence of venous thromboembolism: analysis of 1635 medical cases from the RIETE registry.

Several risk assessment models include infection and immobility among the items to be considered for venous thromboembolism (VTE) prevention. However, information on patients with infection leading to immobility and developing VTE are limited, as well as on the role of specific types of infection. Data were collected from the worldwide RIETE registry, including patients with symptomatic objectively confirmed VTE, and followed-up for at least 3 months. The overall population of RIETE at June 2013 (n = 47,390) was considered. Acute infection leading to immobility was reported in 3.9 % of non-surgical patients. Compared with patients immobilized due to dementia, patients with infection had a shorter duration of immobilization prior to VTE (less than 4 weeks in 94.2 vs. 25.9 % of cases; p < 0.001). During the 3-month follow-up, VTE patients with infection versus those with dementia had a lower rate of fatal bleeding (0.5 vs. 1.1 %; p < 0.05) or fatal PE (1.7 vs. 3.5 %; p < 0.01). Patients with respiratory tract infections had more likely PE as initial VTE presentation than other types of infection (62.3 vs. 37.7 %; p < 0.001). Significantly more patients with pneumonia than those with other respiratory infections had received VTE prophylaxis (50.2 vs. 30.6 %; p < 0.001). Following VTE, patients with sepsis showed a significantly higher risk of fatal bleeding. Based on our real-world data, infection seems to contribute to the pathogenesis of VTE by accelerating the effects of immobility. Its role as VTE risk factor probably deserves further attention and specific assessment in order to optimize VTE prophylaxis and treatment.

[Oxidation Stress Markers Dynamics in the Experiment of Long-Term Antiorthostatic Hypokinesia (Retrospective Study)].

In blood serum of 9 volunteers aged 27 to 42, participated in the experiment with 370-day antiorthostatic hypokinesia (-5 degrees), the lipid peroxidation derivates concentration--diene conjugates (DC), malonic dialdehyde (MDA), Schiff bases (SB) as well as antioxidant defense system indices--tocopherol (TP) concentration and total antioxidative activity level (AOA) were measured. The volunteers were divided into two groups subjected to physical training regimes and used prophylactic measures. In both groups the lipoperoxidation processes initial stages depression (by 54-73%) was observed starting from 50th day, thus the lipid peroxidation final product--SB level was decreased (by 50-61%) only to the 230 day and remains approximately at the same level till the end of the experiment. The restorative period was characterized by decreasing (in 1.6-2.3 times) of MDA and SB concentrations. The decrease in lotal AOA during the aftereffect period was detected in all volunteers, and its level was significantly lower physiological norm range. Probably, long-term adaptation to the simulated weightlessness conditions is accompanied by expressed decrease in biological oxidation processes intensity and significant stress effect, as indicates by essential depression of lipid free radical oxidation in the course of the experiment. At the same time the restorative period after 370-day antiorthostatic hypokinesia was characterized by significantly expressed and prolonged readaptation stress progress. It is evidenced by practically twofold decrease in lipoperoxidation processes intensity against significant increase in TP concentration and water-soluble antioxidants functional reserves exhaustion. Lipid peroxidation activation absence in all terms of examination reflects appropriate compensation of studying impact by volunteers.

PROPRANOLOL PHARMACOKINETICS AND HEMODYNAMIC INDICES IN ANTIORTHOSTATIC HYPOKINESIA.

Purpose of the work was to study pharmacokinetics of beta adrenoblocker propranolol, and hemodynamic indices in volunteers for simulation of some effects of microgravity The study involved 8 essentially healthy subjects and the head-down tilt (-80) bedrest model reproducing the effects of microgravity (BD). This was designed as three series of investigations, i.e. before BD, on BD day-2 and on the first day of BD completion. Propranolol concentration in blood plasma was determined using high performance liquid chromatography with fluorescence detection. Hemodynamic indices including heart rate (HR), stroke volume, cardiac output, cardiac index and total peripheric resistance were measured using integral rheography; average blood pressure (BPav) Was assessed by Korotkovs method. Statistical deviations in propranolol pharmacokinetics were found in none of the three series. The most characteristic reactions to propranolol were BPav reductions in all series and HR decreases 2 hours after intake in the first and second series. These deviations were not pathologic but physiological variations typical of healthy people. Therefore, propranolol can be advised for rational pharmacotherapy of acute cardiovascular diseases in piloted space missions.

Correlation between circulating corticosterone and protein carbonylation in the liver after short-term hypokinesia.

We studied the correlation of the concentration of circulating corticosterone and parameters of dexamethasone suppression test with the level of protein carbonylation in the liver after short-term hypokinesia. Increasing hypokinesia duration was followed by worsening of disturbances in the hypothalamic-pituitary-adrenal system via a negative feedback mechanism and enhanced protein carbonylation in the liver.

[Effect of melatonin on activity of superoxide dismutase (CuZn-SOD) in erythrocytes of patients during short- and long-term hypokinesis]. / Wplyw melatoniny na aktywnosc dysmutazy ponadtlenkowej (CuZn-SOD) w krwinkach czerwonych chorych w okresie hipokinezji krótko- i dlugoterminowej.

INTRODUCTION: Short- or long-lasting hypokinesis is to a large degree the consequence of negative habits of human beings towards a comfortable and more sedentary lifestyle. The period of decreased physical activity can cause disturbance in the balance between systemic processes of the oxidation and reduction, which leads to an increase in reactive oxygen species (ROS) and oxidative stress generation. The aim of the study was to determine the effect of melatonin administration on the cellular superoxide dismutase (CuZn-SOD) activity in red blood cells of patients with short- and long-term hypokinesis as compared to the group of subjects with normal physical activity. MATERIAL AND METHODS: The study included 33 subjects with immobilization. The study group was divided into two subgroups (depending on hypokinesis duration): group A: 15 subjects classified for total hip alloplasty (a short-lasting decrease in physical activity); group B: 18 subjects suffering from multiple sclerosis or the stroke of brain (the long-term hypokinesis). The control group (group C) comprised 17 subjects with normal physical activity. Melatonin was applied at a dose of 5 mg daily, one hour before sleep. The CuZn-SOD activity in red blood cells was determined, according to the Misra and Fridovich method, in two periods: 1) on the first day, 2) on the 10th day (group A), and 30 days (group B) after melatonin administration. RESULTS: A slight increase in CuZn-SOD activity (+3.1%) was observed in group A 10 days after alloplasty and melatonin administration as compared to group B, where a considerable rise in the enzyme activity (+23.3%) was found 30 days after rehabilitation and melatonin supplementation. The average CuZn-SOD activity in both investigative groups was lower than that in the controls (group C). CONCLUSIONS: It was estimated that the short- and long-lasting hypokinesis leads to an increase in ROS generation, what is confirmed by the increase in CuZn-SOD activity. The results of the study on superoxide dismutase activity indicate that oral administration of melatonin for the period of 30 days has a more favorable influence on antioxidative processes than 10-day's melatonin intake.

[Changes in lipid composition of human plasma and erythrocyte membranes due to sodium hydroxybutyrate and normobaric hyperoxia during bed rest].

Gas chromatography was employed to study effects of sodium hydroxybutyrate (GHBA) and normobaric hyperoxia on the fatty-acid composition of total lipids of blood plasma and erythrocyte membranes in 5 normal male volunteers in the baseline data collection period and during 14-d bed rest. Both in plasma and erythrocyte membranes saturated palmitic acid was found increased and polyunsaturated linoleic acid and arachidonic acid reduced.

[The influence of mexidol on the liver functions, structure, and parameters of lipid peroxidation under long-term hypodynamia conditions].

It is established that rabbits kept under the conditions of 30-day hypodynamia with high-grade feeding exhibit disorders in both structure and functions of the liver, which are classified as nonalcoholic type fatness. Other disturbances are an increase in the activity of aspartate aminotransferase (AsAT) and alanine aminotransferase (AlAT) and a decrease in the total protein content predominantly at the expense of albumin. The development of a syndrome of mesenchymal inflammation is manifested by a relative growth of the alpha1, alpha2 and gamma-protein fractions. Pronounced violations of the lipid metabolism were manifested by a growth in the content of beta-lipoproteins, triglycerides, general cholesterol, and low-density lipoproteins and by a decrease in the level of high-density lipoproteins in the blood serum of animals. An increase in the content of malonic dialdehyde was accompanied by a drop in the activity of catalases in the blood serum and erythrocytes of rabbits. Investigation of the morphology of liver tissues showed evidence for small- and large-drop diffuse steatosis, which was most expressed in the central zones of lobes. Using of cytochrome C and mexidol, it is possible to reduce the expression of disorders to various degrees and, in some cases, to prevent the development of pathological changes.

[Cytogenetic characteristics of human blood lymphocytes in vivo in a 120-day bedrest study].

Effects of 120-d bed rest on chromosomal aberration rate were studied in lymphocytes of human peripheral blood in vivo. Chromosomal analysis revealed statistically significant increases in dicentrics and paired acentric fragments in blood lymphocytes of human test-subjects.

[Biochemical diagnosis of immobilization osteoporosis].

The authors have ascertained informative laboratory tests for diagnosis of immobilization osteoporosis and prognostic tests of reparative osteogenesis in its presence. A study was conducted in 97 patients (mean age 39.8 +/- 9.5 years) with bone nonunion and immobilization osteoporosis diagnosed densitometrically (DPXA, Lunar, USA). The proposed procedures are topical if no densitometric study is available and the prediction of osteogenesis on the basis of the phosphatase index is of informative value at the X-ray negative stage (1 month after surgery). The procedures are available and cost-effective; their sensitivity is 75-77%.

The effect of glucocorticoids on bradykinesia induced by immobilization stress.

It is well known that the release of glucocorticoids from the adrenal gland is increased in response to many types of stressors and plays a principal role in stress responses. We have shown that the synthesis of prostaglandins (PGs) in the brain is increased under several stress conditions including immobilization (IMO), and that endogenous glucocorticoids counteract this stress-induced PG synthesis. It was also recently reported that IMO damages dopaminergic (DA) neurons in the substantia nigra (SN), which is known to cause symptoms similar to Parkinson's disease (PD). The present study was therefore undertaken to determine the role of glucocorticoids in modulating the signs of PD induced by IMO. The pole test, in which each mouse was placed head upward at the top of a pole and the time taken to turn downward and to arrive on the floor was recorded, and immunohistochemistry for tyrosine hydroxylase (TH) in the SN were performed to evaluate bradykinesia and injury of DA neurons, respectively. Intact and adrenalectomized (ADX) mice were immobilized for 2 h twice, 1 day apart. Both bradykinesia and a decrease in the number of TH-immunoreactive cells in the SN were observed in ADX mice, but not in intact mice, following IMO. These effects of IMO on ADX mice were restored by treatment with corticosterone or indomethacin, a PG synthesis inhibitor. These results suggest that glucocorticoids play a role in preventing the detrimental effect of IMO on nigral DA neurons and resulting bradykinesia, and that this effect of IMO involves PG-mediated mechanisms.

Phosphate homeotasis in healthy subjects during prolonged periodic and continuous hypokinesia.

OBJECTIVE: This study aimed to show that during hypokinesia (HK), phosphate (P(i)) imbalance increases more with higher than lower physical activity and that P(i) absorption reduces more with higher than lower P(i) imbalance in subjects with higher than lower muscular activity. METHODS: Studies were conducted on 30 healthy male subjects during 364 days of HK. They were equally divided in three groups: unrestricted active control subjects (UACS), continuously hypokinetic subjects (CHKS) and periodically hypokinetic subjects (PHKS). CHKS were kept under average walking distances of 0.5+/-0.2 km day(-1) PHKS were kept under average walking distances of 0.5+/-0.1 and running average distances of 8.7+/-1.2 km day(-l) for 5 days and 2 days per week, respectively. UACS were placed under average running distances of 8.7+/-1.2 km day(-l). RESULTS: P(i) imbalance, serum, urine and fecal P(i) levels, and urine and serum calcium (Ca(2+)) levels increased significantly (p<0.05) and P(i) absorption, and serum intact parathyroid hormone (iPTH) and 1,25-dehydroxyvitamin D (1,25 (OH)(2) D(3)) levels decreased significantly (p<0.05) in CHKS and PHKS compared with their pre-HK values and their respective active control (UACS). However, the P(i) imbalance, serum, urine and fecal P(i) levels, and serum and urine Ca(2+) levels increased more significantly (p<0.05), and P(i) absorption and serum iPTH and 1,25 (OH)(2) D(3) levels decreased more significantly in PHKS than in CHKS. CONCLUSIONS: Higher P(i) imbalance with higher than lower physical activity shows that the risk of higher P(i) imbalance is inversely related to the intensity of physical activity. Lower P(i) absorption with higher than lower P(i) imbalance shows that the risk of lower P(i) absorption is inversely related to magnitude of P(i) imbalance. In conclusion P(i) imbalance increases more with higher than lower physical activity and that P(i) absorption decreases more with higher than lower P(i) imbalance indicating that during HK the use of P(i) decreases more with higher than lower physical activity.

Electrolyte homeostasis in trained and untrained healthy subjects during prolonged hypokinesia.

OBJECTIVE: This study aimed to show that during hypokinesia (HK) electrolyte imbalance increases more in trained than untrained subjects and that electrolyte loss increases more with higher than lower electrolyte imbalance in trained than untrained subjects. METHODS: Studies were conducted during 364-day HK. Subjects were equally divided in four groups: trained ambulatory control subjects (TACS), trained hypokinetic subjects (THKS), untrained ambulatory control subjects (UACS) and untrained hypokinetic subjects (UHKS). THKS and UHKS were limited to average walking distances of 0.5+/-0.1 km day(-1). TACS were running average distances of 9.8+/-1.3 and UACS were walking average distances of 1.8+/-0.2 km day(-1). RESULTS: Plasma potassium (K(+)), calcium (Ca(+2)) and magnesium (Mg(+2)) levels, urine and fecal electrolyte excretion, electrolyte imbalance, plasma aldosterone (PA) and plasma rennin activity (PRA) increased significantly (p<0.05), while electrolyte absorption, plasma intact parathyroid hormone (iPTH) and dihydroxyvitamin D (1,25 (OH)(2) D(3)) levels decreased significantly (p<0.05) in THKS and UHKS compared with their pre-HK values and their respective controls (TACS and UACS). Electrolyte imbalance, plasma electrolyte levels, urine and fecal electrolyte excretion, PA and PRA levels increased more significantly (p<0.05), while electrolyte absorption, plasma iPTH and 1, 25 (OH)(2) D(3) levels decreased more significantly (p<0.05) in THKS than in UHKS. CONCLUSION: The higher electrolyte imbalance in trained as compared to untrained subjects shows that the risk of higher electrolyte imbalance is inversely related to the magnitude of physical conditioning. The higher electrolyte loss with higher than lower electrolyte imbalance shows that the risk of higher electrolyte loss is inversely related to the magnitude of electrolyte imbalance. In conclusion electrolyte imbalance increases more in trained than untrained subjects and that electrolyte loss increase more with higher than lower electrolyte imbalance indicating that during prolonged HK the use of electrolytes decreases more with higher than lower physical conditioning.

[Effects of antiorthostatic hypokinesia on blood levels of interleukine-1beta and interleukine-6 in primates].

Investigations with Macaca mulatta of 4-5 yrs. of age with the body mass of 4.5-6.5 kg showed that 10 days of tilting with the head end at .5 degrees reduced body temperature but not levels of interleukine-1beta and interleukine-6 in blood plasma. On the next days after return of animals to cages IL-6 was found to increase sharply in more than 10 times. On subsequent 4 days both IL -1beta and IL-6 were within the normal range.

Effect of age-related chronic immobility on markers of bone turnover.

UNLABELLED: The effects of acute immobilization on bone turnover are well known, but the effects of chronic hypomobility with aging have not been studied. In a cohort of 1064 frail elderly subjects, immobility was significantly associated with serum PINP but not serum CTx after adjusting for confounders. The effect of immobility may be more marked on bone formation than on bone resorption. INTRODUCTION: Accelerated bone turnover and rapid bone loss caused by acute immobilization is well recognized, but the effects of age-related chronic reduction in mobility on bone turnover have been less well studied. We assessed the associations between bone turnover and measures of mobility in a cohort of elderly subjects. MATERIALS AND METHODS: We measured serum levels of the aminoterminal propeptide of type I collagen (PINP), a marker of bone formation, and serum concentrations of the carboxyterminal telopeptide of type I collagen (CTx), a marker of bone resorption, as well as serum intact PTH, serum 25 hydroxyvitamin D (25OHD), mobility, and static balance in a well-characterized sample of 1064 elderly men and women living in residential aged care facilities. Serum creatinine, phosphate, albumin, and calcium were measured in a randomly selected subgroup of 447 subjects. RESULTS: The subjects were elderly and frail; their mean age was 86.0 years (range, 65-101 years); 69% used a walking aid; and 77% were vitamin D deficient (serum 25OHD level < 39 nM). Both serum PINP and CTx increased with age in both sexes. Elevated PINP or CTx was significantly correlated with high PTH, creatinine, and albumin in both genders, except for albumin in women. Age- and gender-adjusted serum CTx and PINP were significantly higher in those with poorer mobility and those with worse static balance. In multivariate analyses, higher serum PINP but not CTx was associated with poorer mobility and worse static balance. CONCLUSIONS: Our findings suggest that poor mobility contributes to the state of accelerated bone turnover usually seen in the elderly. The effect of chronic relative immobility may be more marked on bone formation than bone resorption.

Tissue magnesium loss during prolonged hypokinesia in magnesium supplemented and unsupplemented rats.

This study aims at showing that during hypokinesia (HK) tissue magnesium (Mg2+) content decreases more with higher Mg2+ intake than with lower Mg2+ intake and that Mg2+ loss increases more with higher than lower tissue Mg2+ depletion due to inability of the body to use Mg2+ during HK. Studies were conducted on male Wistar rats during a pre-HK period and a HK period. Rats were equally divided into four groups: unsupplemented vivarium control rats (UVCR), unsupplemented hypokinetic rats (UHKR), supplemented vivarium control rats (SVCR) and supplemented hypokinetic rats (SHKR). SVCR and SHKR consumed 42 mEq Mg2+ per day. The gastrocnemius muscle and right femur bone Mg2+ content decreased significantly, while plasma Mg2+ level and urine and fecal Mg2+ loss increased significantly in SHKR and UHKR compared with their pre-HK values and their respective vivarium controls (SVCR and UVCR). However, muscle and bone Mg2+ content decreased more significantly and plasma Mg2+ level, and urine and fecal Mg2+ loss increased more significantly in SHKR than in UHKR. The greater tissue Mg2+ loss with higher Mg2+ intake and the lower tissue Mg2+ loss with lower Mg2+ intake shows that the risk of higher tissue Mg2+ depletion is directly related to the magnitude of Mg2+ intake. The higher Mg2+ loss with higher tissue Mg2+ depletion and the lower Mg2+ loss with lower Mg2+ tissue depletion shows that the risk of greater Mg2+ loss is directly related to the magnitude of tissue Mg2+ depletion. It was concluded that tissue Mg2+ depletion increases more when the Mg2+ intake is higher and that Mg2+ loss increases more with higher than lower tissue Mg2+ depletion indicating that during prolonged HK the tissue Mg2+ depletion is not due to the Mg2+ shortage in food but to the inability of the body to use Mg2+.

Felbamate reduces hormone release and locomotor hypoactivity induced by repeated stress of social defeat in mice.

Glutamatergic neurotransmission plays a role in stress hormone release and the development of mood diseases. The aim of these studies was to verify the hypothesis that repeated treatment with felbamate, an antiepileptic drug modulating glutamatergic neurotransmission, affects hormone release in response to chronic stress. A mouse model of repeated social defeat (nonaggressive male mouse repeatedly defeated by aggressive counterparts) was used. The results showed that acute treatment with felbamate reduced hypolocomotion in an open field induced by repeated social conflict. The same stress procedure resulted in increased release of corticosterone and dopamine. Felbamate decreased noradrenaline concentrations and inhibited stress-induced rise in corticosterone and dopamine. It is suggested that modulation of stress hormone release may be induced by the action of felbamate on glutamate neurotransmission, and neuroendocrine changes could contribute to behavioural effects of the drug. Antidepressant action of this mood-stabilizing drug suggested by clinicians needs further verification.

[The red blood system in men during long-term head-down bed rest].

Red blood was analyzed in six 25 to 40 yr. old male volunteers in a 120-d head-down bedrest (HDBR) study. The hematological investigation included morphological analyses (erythrocyte count and hemoglobin), and determination of iron turnover, erythrocyte IgA, IgG and IgM, metabolism, lipids and phospholipids, and lipid peroxidation rate (LPO). At the beginning of HDBR (day 7), the erythrocyte count and hemoglobin content were found increased w/o any visible changes in the other parameters. Further exposure to HDBR (days 50-100) resulted in modification of intracellular metabolism in erythrocytes, increases in serum iron, and serum and erythrocyte ferritin. On HDBR days 50 and 100, and post-HDBR day 9, cholesterol was increased, LPO intensified and antioxidant activities inhibited, which suggested destabilization of the cell membrane. Hematological shifts in the bedrested volunteers were of the type and pattern similar to those in cosmonauts who fulfilled extended space missions.

[The relationship of changes in blood fatty acids and calcium during 370-day head-down bed rest].

Serum calcium and serum and erythrocyte higher fatty acids (HFA) in 8 male subjects in a 370-d head-down bed rest experiment were different in group-A (applying preventive physical training and pharmacy) and group-B (control). On day 46 of the experiment, HFA content in all lipid fractions decreased sharply in both groups; however, HFA level in serum exceeded baseline values in 2-6 times and remained low in erythrocytes. Difference between the groups became appreciable on HDT day 110.