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.

[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.

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.

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.

Selenium reduces bradykinesia and DNA damage in a rat model of Parkinson's disease.

OBJECTIVE: The aim of this study was to explore the effects of selenium (Se) on locomotor activity and DNA damage in a rat model of Parkinson's disease (PD) induced by paraquat (PQ). METHODS: Forty-eight male Wistar rats were divided into four groups: control group (n = 12), Se group (n = 12), PQ group (n = 12), and Se + PQ group (n = 12). PQ was administered intraperitoneally (10 mg/kg). Se was offered in the drinking water at a concentration of 11.18 µg/L. Locomotor activity was evaluated weekly using the narrow beam test. The comet assay was performed to assess the level of DNA damage in leukocytes and in brain cells. RESULTS: As expected, increased DNA damage was found in the PQ group compared with the control and Se groups (P < 0.001). Interestingly, coadministration of Se and PQ effectively prevented the harmful effects of the toxin in locomotor activity and at the molecular level, reducing bradykinesia (P < 0.01) and DNA damage in leukocytes compared with the PQ-only group (P < 0.001), whereas the levels of DNA damage were comparable to those found in the control and Se groups (P > 0.05). Using the comet assay to analyze brain cells, no differences were found between the groups with regard to damage index (P = 0.774), damage frequency (P = 0.817), or non-detectable cell nuclei (P = 0.481). CONCLUSION: In this experimental model of PQ-induced PD, the use of Se could contribute to the maintenance of locomotor activity and the integrity of leukocytes DNA. No changes in the levels of DNA damage in brain cells were observed between the experimental groups.

Blood metal concentrations of manganese, lead, and cadmium in relation to serum ferritin levels in Ohio residents.

The objectives of this study were to assess ferritin-specific profiles of blood metal concentrations such as manganese, lead, and cadmium and to evaluate whether ferritin may affect the behavior of the blood metals in relation to menstruation, menopause, or sex in Ohio residents. Recruited participants included residents from Marietta, East Liverpool, and Mt. Vernon, OH, USA, who were aged 30-75 years and lived at least 10 years in their respective town. The levels of the neurotoxic metals such as manganese, cadmium, and lead were assayed in whole blood. Serum was analyzed for ferritin level [as a biomarker of iron (Fe) status]. An association between blood metal concentrations and independent variables (age, serum ferritin, manganese exposure status, and sex) by multiple regression analysis was assessed, controlling for various covariates such as BMI, educational level, smoking, and alcohol drinking status. Overall, the geometric means of blood manganese, cadmium, and lead levels of all participants (n = 276) were 9.307 µg/L, 0.393 µg/L, and 1.276 µg/dL, respectively. Log serum ferritin concentrations were inversely associated with log blood manganese concentration (ß = -0.061 log ferritin and ß = 0.146 categorical ferritin) and log blood cadmium concentrations (ß = -0.090 log ferritin and ß = 0.256 categorical ferritin). Log serum ferritin concentrations were not associated with log blood lead concentrations. Variables of age, sex, and exposure status were not associated with log manganese concentrations; however, log blood cadmium concentrations were higher in older population, women, and smokers. Log blood lead concentrations were higher in older population, men, and postmenopausal women. Our study showed that iron deficiency is associated with increased levels of blood manganese and cadmium, but not blood lead, in Ohio residents. These metals showed different toxicokinetics in relation to age, sex, and menopausal status despite similar relationships between ferritin and metal concentrations.

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.

Chronic periodic fluid redistribution effect on muscle calcium in healthy subjects during prolonged hypokinesia.

Studies have shown that chronic periodic fluid shifting upwards is not sensed as excessive fluid volume and excretion mechanisms are not activated. To determine if chronic periodic fluid and volume shifting upwards can affect muscle calcium (Ca(2+)) during hypokinesia (HK) we measured muscle Ca(2+) content, plasma Ca(2+) concentration, and Ca(2+) losses in urine and feces. Studies were conducted on 40 healthy male volunteers. They were divided into four equal groups: active control subjects (ACS), hypokinetic subjects (HKS), periodic fluid redistribution control subjects (PFRCS), and periodic fluid redistribution hypokinetic subjects (PFRHS). Plasma Ca(2+) level decreased (p < 0.05) in Ca(2+) repleted muscle, muscle Ca(2+) level increased (p < 0.05), and Ca(2+) losses in urine and feces decreased (p < 0.05) in the PFRHS group compared with the HKS group. Plasma Ca(2+) level increased (p < 0.05) in Ca(2+) deficient muscle, muscle Ca(2+) level decreased (p < 0.05), and Ca(2+) losses in urine and feces increased (p < 0.05) in the HKS group compared with their pre-experimental levels and the values in their respective control groups (ACS and PFRCS). This study shows that the muscle Ca(2+) content increases and Ca(2+) excretion decreases, suggesting the clinical potential of chronic periodic fluid and volume redistribution in treatment of muscle Ca(2+) deficiency.

Muscle potassium and potassium losses during hypokinesia in healthy subjects.

Hypokinesia (HK) induces electrolyte losses in electrolyte-deficient tissue, yet the mechanisms of electrolyte losses in electrolyte-deficient tissue remain unknown. Mechanisms of electrolyte deposition could be involved. To determine the effect of prolonged HK on potassium (K+) deposition were measured muscle K+ content and K+ losses. Studies were conducted on 20 physically healthy male volunteers during 30 days pre-experimental period and 364 days experimental period. Subjects were equally divided into two groups: control subjects (CS) and experimental subjects (ES). The CS group was run average distances of 9.8±1.7 km day(-1) and the ES group was walked average distances of 2.7±0.6 km day(-1). Muscle K+ content decreased (p<0.05) and plasma K+ concentration, and K+ losses in urine and feces increased (p<0.05) in the ES group compared to their pre-experimental level and the values in their respective CS group. Muscle K+ content, plasma K+ level, and urine and fecal K+ losses did not show any changes in the CS group compared to their pre-experimental values. The conclusion was that K+ losses in K+-deficient muscle of healthy subjects could have been attributable to the less efficient K+ deposition inherently to prolonged HK.

[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.

[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.

Muscle calcium metabolic effects of hypokinesia in physically healthy subjects.

The incompleteness of electrolyte deposition during hypokinesia (HK; diminished movement) is the defining factor of electrolyte metabolic changes, yet the effect of prolonged HK upon electrolyte deposition is poorly understood. The objective of this investigation was to determine the effect of muscle calcium (Ca(++)) changes upon Ca(++) losses during prolonged HK. Studies were conducted on 20 physically healthy male volunteers during a pre-experimental period of 30 days and an experimental period of 364 days. Subjects were equally divided in two groups: control subjects (CS) and experimental subjects (ES). The CS group ran average distances of 9.2 ± 1.2 km day(-l), and the ES group walked average distances of 2.3 ± 0.2 km day(-l). Muscle Ca(++) contents, plasma Ca(++) concentrations, and Ca(++) losses in urine and feces were measured in the experimental and control groups of subjects. The muscle Ca(++) contents decreased (p < 0.05), and plasma Ca(++) levels and Ca(++) losses in the urine and feces increased (p < 0.05) in the ES group compared with their pre-experimental levels and the values in their respective CS group. Muscle Ca(++) contents and plasma Ca(++) levels and urinary and fecal Ca(++) losses did not change in the CS group compared to their pre-experimental levels. It is concluded that prolonged HK increase plasma Ca(++) concentrations and Ca(++) losses in Ca(++) deficient muscle indicating decreased Ca(++) deposition.

[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.

[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%.

[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.

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.