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Relation of intracellular K+ and steroidogenesis in isolated adrenal zona glomerulosa and fasciculata cells.

1. Intracellular K+ content, water spaces and corticosterone output were measured in isolated zona glomerulosa and zona fasciculata-reticularis cell suspensions of rat adrenal cortex, after incubation in vitro under conditions designed to alter steroidogenesis. 2. Intracellular K+ of unpurified zona glomerulosa cells was not altered after stimulation of corticosterone output with serotonin. Similarly, with zona glomerulosa cells purified by unit gravity sedimentation, no change in intracellular K+ was detected after stimulation of steroidogenesis with serotonin or angiotensin II. 3. In high-potassium medium (final concentration 8.4 mmol/1), parallel increases in intracellular K+ and corticosterone output were observed with both purified zona glomerulosa cells. However, a similar increase in intracellular K+ also occurred in high-potassium medium with zona fasciculata cells, whose steroid output is unresponsive to external potassium concentration ([K+]). 4. Ouabain at 10(-5) mol/1 depressed the intracellular [K+] of glomerulosa cells but did not alter basal or stimulated corticosterone output. Similar results were obtained with fasciculata cells. 5. Ouabain at 5 times 10(-4) mol/1 further depressed intracellular [K-+] of glomerulosa cells and inhibited basal and stimulated corticosterone output. However, this concentration of ouabain also inhibited steroidogenesis in fasciculata cells. 6. These results demonstrate a variety of situations where changes in intracellular [K+] are dissociated from those in corticosterone output and indicate that intracellular [K+] cannot be the sole mechanism regulating steroidogenesis under these conditions.

Adrenal Cortex↗

Simulation analysis of muscle activity changes with altered body orientations during pedaling.

Testing hypotheses related to the effect of gravitational orientation on neural control mechanisms is difficult for most locomotor tasks, like walking, because body orientation with respect to gravity affects both sensorimotor control and task mechanics. To examine the mechanical effect of body orientation independently from changes in workload and posture, Brown et al. (J. Biomech. 29 p. 1349, 1996) studied pedaling at altered body orientations. They found that subjects pedaling at different orientations changed needlessly their muscle excitations, putatively to preserve body-upright pedaling kinematics. We tested the feasibility of this hypothesis using simulations based on a three biomechanical-function pair organization for control of lower limb muscles (limb extension/flexion pair, extension/flexion transition pair, and foot plantarflexion/dorsiflexion pair), where each pair consists of alternating agonistic/antagonistic muscles. Adjustment of only three parameters, one to scale the muscle excitations of each pair, was sufficient to preserve pedaling kinematics to altered body orientation. Because these adjustments produced changes in muscle excitation and net joint moments similar to those observed in pedaling subjects, the hypothesis is supported. Moreover, the effectiveness of a decoupled gain adjustment procedure where each parameter was adjusted by error in only one aspect of the pedaling trajectory during each iteration (i.e., cadence adjusted the Ext/Flex parameter; peak-to-peak variation in crank velocity over the cycle adjusted the transition parameter; average ankle angle over the cycle adjusted the foot parameter) further supports the distinct function of each muscle pair.

Bicycling↗

EMG-activity and muscular performance of lower leg during stretch-shortening cycle after cooling.

To test the effect of cooling on EMG-activity of muscles working as an agonist and antagonist in the lower leg, 12 men dressed in shorts and jogging shoes performed a drop-jump exercise after 60 min exposures to 27 degrees C and 10 degrees C. Cooling decreased mean skin temperature 5.6 +/- 0.4 degrees C (mean +/- SD, P < 0.001), whereas rectal temperature was unaffected. The muscle temperature measured from m. gastrocnemius medialis decreased 4.1 +/- 0.3 degrees C (P < 0.01) at the depth of 30 mm below skin surface. To find the optimal stretching velocity for potentiation of elastic energy, the drop-jump exercise was performed from six different bench heights (10, 20, 30, 40, 50, and 60 cm). The optimal velocity was not altered on account of cooling. In cooled subjects during the stretch phase of the drop jumps the EMG-activity of m. triceps surae complex (agonist) increased (P < 0.05-0.001) while the activity of m. tibialis anterior (antagonist) remained unchanged. After cooling during the shortening phase of the jumps the EMG-activity of m. triceps surae complex decreased (P < 0.05-0.001), whereas the activity of m. tibialis anterior increased (P < 0.05-0.001). In addition, after cooling the peak EMG-activity appeared on the average 28 ms earlier, which shifted the peak activity from the shortening phase (at 27 degrees C) to the stretch phase (at 10 degrees C). Cooling increased the mean duration of stretch and shortening phases by 28 +/- 3 ms (P < 0.001) and 23 +/- 2 ms (P < 0.001), respectively. The average force production during the shortening phase was 26% less (P < 0.05) after cooling, which resulted in a decreased rise of body centre of gravity (P < 0.05-0.01). It is concluded that during a stretch-shortening cycle cooling alters the EMG-activity of agonist and antagonist muscles on a contradictory manner and results in an earlier peak EMG-activity. Therefore, alterations in motor unit recruitment could be responsible for the prolonged muscle contraction and decreased force production on account of cooling.

Adult↗

The alteration of plasma lipoproteins by cremophor EL.

Cremophor EL (CRM) is a non-ionic amphipathic emulsifier which has been used as a parenteral vehicle for many hydrophobic drugs. At concentrations above 0.4 mg ml-1, CRM alters lipoproteins so as to reduce their electrophoretic mobility; high density lipoprotein (HDL) is somewhat more sensitive than low density lipoprotein (LDL) in this regard. The same phenomenon was observed with Triton X-100 and Tween-80, two other non-ionic detergents. Ultracentrifugation experiments show that CRM alters the density of HDL resulting in a product with approximately the same specific gravity as LDL. Administration of mesoporphyrin solubilized with CRM to the mouse resulted in a rapid clearance of porphyrin bound to this new HDL species. Such a phenomenon may account for reports which indicate that CRM promotes the distribution of photosensitizing agents to neoplastic tissues.

Animals↗

[Limitations in the opening of the mouth of an arthrogenic nature].

Mouth opening limitations of arthrogenous nature are subdivided according to a personal schedule into indirect and direct types. The former are brought on by occlusal alterations: these affect articular remodelling and may cause anatomical and functional changes of varying gravity in the temporo-mandibular joint with consequent limitations on opening movements. The latter are the consequence of various pathogenic agents (traumatic, neoplastic, inflammatory, degenerative) originating within the articular structures and developing therein, progressively limiting their function. Some significant personal cases are reported and on the basis of the series the aetiopathogenetic problems of the various forms are discussed, with emphasis on those which represent the basic criteria for therapy.

Adolescent↗

[Morphofunctional state of the heart in dilated cardiomyopathy in children].

To study the morphofunctional state of the heart, 49 children aged 1 to 15 years with dilated cardiomyopathy (DCMP) were examined. The diagnosis was established on the basis of comprehensive clinical and instrumental examinations. It was discovered as a result of echocardiography that children with dilated cardiomyopathy show considerable dilatation of the cardiac chambers, accompanied by moderate hypertrophy of the myocardium (mainly of the left ventricle) and by appreciable impairment of the function of myocardial contraction and relaxation together with derangement of heart pump function. The overwhelming majority of patients with DCMP manifested relative failure of the mitral valve which plays an important role in the impairment of intracardiac and central hemodynamics. It should be noted that echographic alterations seen in DCMP are not specific. However, they provide an idea of the gravity of heart damage, that is of importance in outlining the policy of treatment and prophylactic measures.

Adolescent↗

[Prognostic significance of ECG changes in acute pneumonia].

A total of 293 patients with acute pneumonia were examined for the relationship between ECG changes and the gravity and immediate outcomes of disease. The pneumonia gravity was determined by the mathematic method based on the computation of the prognostic index of pneumonia (Z. K. Trushinsky et al., 1978). It was established that the overload of the right atrium, malfunction of automatism, excitability and conduction, depression of the ST segment and T wave inversion were in a good agreement with the gravity of pneumonia. In patients with severe and medium-severe disease, the above alterations were more demonstrable than in patients with mild pneumonia. Atrial fibrillation and intraventricular blockades, hypertrophy of the left ventricle and changes in the end part of the ventricular complex were observed more frequently in patients discharged from the hospital with residual phenomena as compared to the recovered patients. This indicates a prognostically unfavourable importance of the ECG signs while evaluating the immediate prognosis. In patients with associated acute pneumonia and coronary heart disease, the ECG changes (arrhythmias, displacement of the ST segment and T wave inversion) were more pronounced and steadier, which was linked with the development of more profound dystrophic lesions of the myocardium.

Acute Disease↗

Crickets in space: morphological, physiological and behavioral alterations induced by space flight and hypergravity.

"Crickets in Space" was a Neurolab experiment by which the balance between genetic programs and the gravitational environment for the development of a gravity sensitive neuronal system was studied. The model character of crickets was justified by their external gravity receptors, identified position-sensitive interneurons (PSI) and gravity-related compensatory head response, and by the specific relation of this behavior to neuronal arousal systems activated by locomotion. These advantages allowed to study the impact of modified gravity on cellular processes in a complex organism. Eggs, 1st, 4th and 6th stage larvae of Acheta domesticus were used. Post-flight experiments revealed a low susceptibility of the behavior to micro- and hypergravity while the physiology of the PSI was significantly affected. Immunocytological investigations revealed a stage-dependent sensitivity of thoracic GABAergic motoneurons to 3 g-conditions concerning their soma sizes but not their topographical arrangement. The morphology of neuromuscular junctions was not affected by 3 g-hypergravity. Peptidergic neurons from cerebral sensorimotor centers revealed no significant modifications by microgravity (micro g). The contrary physiological and behavioral results indicate a facilitation of 1 g-readaptation originating from accessory gravity, proprioceptive and visual sense organs. Absence of anatomical modifications point to an effective time window of micro g or 3 g-expo-sure related to the period of neuronal proliferation. The analysis of basic mechanisms of how animals and man adapt to altered gravitational conditions will profit from a continuation of the project "Crickets in Space".

Adaptation, Physiological↗

Selected contribution: redistribution of pulmonary perfusion during weightlessness and increased gravity.

To compare the relative contributions of gravity and vascular structure to the distribution of pulmonary blood flow, we flew with pigs on the National Aeronautics and Space Administration KC-135 aircraft. A series of parabolas created alternating weightlessness and 1.8-G conditions. Fluorescent microspheres of varying colors were injected into the pulmonary circulation to mark regional blood flow during different postural and gravitational conditions. The lungs were subsequently removed, air dried, and sectioned into approximately 2 cm(3) pieces. Flow to each piece was determined for the different conditions. Perfusion heterogeneity did not change significantly during weightlessness compared with normal and increased gravitational forces. Regional blood flow to each lung piece changed little despite alterations in posture and gravitational forces. With the use of multiple stepwise linear regression, the contributions of gravity and vascular structure to regional perfusion were separated. We conclude that both gravity and the geometry of the pulmonary vascular tree influence regional pulmonary blood flow. However, the structure of the vascular tree is the primary determinant of regional perfusion in these animals.

Animals↗

Altered behaviour of hamsters by prolonged hypergravity: adaptation to 2.5 G and re-adaptation to 1 G.

We studied the functional adaptation process in 40 hamsters subjected to either prolonged hypergravity to normal gravity. Subadult golden hamsters (n = 20) exposed to a hypergravity condition of 2.5 G for 6 months were tested to investigate the effect of hyper gravity on the perceptive motor skills and compared with control hamsters (n = 20). The motor coordination of the hypergravity hamsters hardly changed; locomotion was normal and swimming was possible. Equilibrium maintenance was disturbed during the first 3 months as was shown by the higher crossing time (p < 0.001) and higher fall frequency (p < 0.001) for the hypergravity group. Significant differences were also found in orientation during swimming (p = 0.007) and turning behaviour in the rotation task (p < 0.001) and in the no-rotation task (p = 0.029). After 6 months, 10 hamsters of both groups were tested for another 4 months, also the hypergravity hamsters were living at 1 G. Differences in orientation in the two groups did not change during swimming and turning behaviour during the rotation task (p = 0.026). Based on our findings, we conclude that the hamsters functionally adapted to hypergravity, which led to an altered performance of several tasks. The condition continued after 4 months of normal gravity.

Animals↗

Effect of gravity in long-term vitreous tamponade: in vivo investigation using perfluorocarbon liquids and semi-fluorinated alkanes.

PURPOSE: In order to investigate whether gravity is the reason for retinal degeneration in long-term vitreous tamponade, perfluorohexyloctane (F6H8), perfluorodecalin (PFD), and a mixture of F6H8/PFD were compared. MATERIALS AND METHODS: Each group of 5 rabbits received a 3-month tamponade with either PFD (pure) (1.93 g/cm(3)), F6H8 (pure) (1.33 g/cm(3)), or a 1:1 mixture of F6H8/PFD (1.62 g/cm(3)). Electroretinograms (ERG) were performed pre- and postoperatively. Lower and upper retinal areas were compared using immunohistochemical methods. Transmission electron microscopy was performed to investigate alterations in the photoreceptors. RESULTS: All three substances were tolerated well in rabbit eyes for up to 3 months. Dispersion was seen earliest with PFD and latest with pure F6H8. None of the substances demonstrated inflammatory reactions or vascular alterations. ERGs were not considerably altered with any of the substances. Histology of the retina showed alterations in the cell counts within the inner and outer nuclear layer that were not attributable to the gravity of the tamponading agent. CONCLUSION: In contrast to previously published work, this study did not detect any tamponade-related structural damage of the retina after a 3-months tamponade in the rabbit model. Based upon this study, we conclude that gravity might not be causally linked to retinal damage.

Animals↗

The molecular chaperone HSP47 rapidly senses gravitational changes in myoblasts.

Skeletal muscle unloading induced by spaceflight or bed rest leads to muscle atrophy. It is unclear how muscle atrophy is caused and how muscles respond to microgravity. We addressed the response of collagen and its chaperone system to gravitational forces. We show here that expression of HSP47, a collagen-specific molecular chaperone, responds to gravitational changes, including microgravity and hypergravity in vitro and in vivo. By using the method hindlimb suspension of rats, which mimics microgravity conditions, we demonstrated that the expression of Hsp47 mRNA decreased within 1 day and the mRNA levels of collagen types I and IV were subsequently reduced. In contrast, hypergravity stimulated HSP47 expression. HSP47 and collagen types I and IV were localized intracellularly in the endoplasmic reticulum and/or Golgi apparatus of myoblasts, as expected. Intriguingly, Hsp47 mRNA levels in cultured myoblasts increased significantly with hypergravity treatment at 40G for 2 h, and decreased with microgravity treatment at almost 0G for 1-2 h. Collagen mRNA levels were also altered, although changes were slower and less pronounced compared with those for HSP47. The gravity-regulated HSP47 may play a role in the maintenance of the extracellular matrix by modulating collagen production at the primary stage of adaptation.

Animals↗

Microgravity and the lung.

Although environmental physiologists are readily able to alter many aspects of the environment, it is not possible to remove the effects of gravity on Earth. During the past decade, a series of space flights were conducted in which comprehensive studies of the lung in microgravity (weightlessness) were performed. Stroke volume increases on initial exposure to microgravity and then decreases as circulating blood volume is reduced. Diffusing capacity increases markedly, due to increases in both pulmonary capillary blood volume and membrane diffusing capacity, likely due to more uniform pulmonary perfusion. Both ventilation and perfusion become more uniform throughout the lung, although much residual inhomogeneity remains. Despite the improvement in the distribution of both ventilation and perfusion, the range of the ventilation-to-perfusion ratio seen during a normal breath remains unaltered, possibly because of a spatial mismatch between ventilation and perfusion on a small scale. There are unexpected changes in the mixing of gas in the periphery of the lung, and evidence suggests that the intrinsic inhomogeneity of the lung exists at a scale of an acinus or a few acini. In addition, aerosol deposition in the alveolar region is unexpectedly high compared with existing models.

Humans↗

The effects of posture on capillary blood flow pulse and gas exchange in the lungs of man.

Cardiac output and pulmonary capillary blood flow were measured on 5 normal subjects to dye dilution and N2O-body plethysmograph method, respectively. To facilitate calculations and to improve signal to noise ratio, a computer of average transient was used. Cardiac output increased from 7.16 +/- SEM 0.86 L/min to 8.46 +/- 0.72 L/min after the subject changed his posture from upright to supine. Pulmonary capillary blood flow also increased from 5.2 +4- 0.44 L/min to 6.95 +/- 0.48 L/min. These changes were mostly due to changes in stroke volume. The differences between cardiac output and pulmonary capillary blood flow were 19% and 15% in upright and supine positions, respectively. Conduction time of blood flow pulse from pulmonic valve to pulmonary capillary beds prolonged significantly in supine position. Flow acceleration and pulsatility index did not change by posture. Changes in flow acceleration and changes in PaO2 were significantly correlated. These results indicate: 1) profiles of pulmonary capillary blood flow pulse do not alter by posture except conduction time, 2) zone I which is normally closed because of gravity in upright position seems to recruit in supine position, and 3) blood flow acceleration is responsible at least partially for postural changes in PaO2.

Adult↗

Human cardiovascular response to sympathomimetic agents during head-down bed rest: the effect of dietary sodium.

Changes in sympathoadrenal function and cardiovascular deconditioning have long been recognized as a feature of the physiological adaptation to microgravity. The deconditioning process, coupled with altered hydration status, is thought to significantly contribute to orthostatic intolerance upon return to Earth gravity. The cardiovascular response to stimulation by sympathomimetic agents before, during, and after exposure to simulated microgravity was determined in healthy volunteers equilibrated on normal or high sodium diets in order to further the understanding of the deconditioning process.

Adult↗

Microbiological problems of manned space flight.

The hazard of infectious disease in long-duration manned space flight is discussed in relation to the unique conditions of spacecraft environment. Confinement in a small, enclosed volume, special problems of waste disposal and personal hygiene, zero gravity, and high oxygen content present special features that favor transmission of micro-organisms. Alterations in microbial flora will occur and these will influence host defenses against disease. Genetic variants of micro-organisms could be induced by and selected under the unique conditions of space flight. A reduction in the variety of microbial flora could result in "microbial shock" on re-entry. The influence of environmental conditions of the spacecraft on host defenses against infection is unpredictable in the absence of investigative work. However, pre-flight assessment of immune status is recommended. A graduated pre-flight isolation period is highly recommended to permit exchange of flora, to protect astronauts from new agents, and to allow most infections to emerge.

Aerospace Medicine↗

[Hormonal regulation of metabolism in the human body in microgravity and during simulation of its physiological effects].

The paper presents results of investigations into the effects of space flight and simulation experiments of various length on the hormonal regulation of metabolism in the human body. Microgravity was shown to instigate shifts on different levels of the hormonal regulation and consequent adjustment of metabolism to this new environment. For instance, adaptation occurs on the level of basal secretory activity resulting in altered metabolism and formation of a pool of hormones. Metabolism readaptation to the Earth's gravity is dependent on polymorphic processes in the system of hormonal regulation developing in the course of time. Trends in the hormonal regulation of water-electrolyte metabolism during early adaptation point to inequality of contributions of the antidiuretic hormone, natriuretic peptide, and the renin-angiotensin-aldosterone system. In the ground-based simulations responses of the hormonal regulation of water-electrolyte metabolism differ in intensity and types of hormones involved. Temperature variation can modify reactions of the comosis and volume regulating hormones at the beginning of adaptation. Physical-chemical regulation of calcium homeostasis in microgravity reveals itself by a rapid decline of the calcium-binding ability of blood buffers and, later on, degradation of the relative ability of extraplasmic structures to bind calcium. Qualitative and quantitative changes in the diurnal rhythm of the suprarenal steroidogenesis are indicative of modification of intensity of reactions of the main biosynthetic sequences. Countermeasures used by test-subjects in these investigations loosened significantly the aldosterone-secreting biosynthetic sequences but were favorable to the synthesis of testosterone and hydrocortisone. Some of the highly variable processes of hormonal regulation were mute to the diurnal rhythms in the pre-flight and preexperimental periods.

Adaptation, Physiological↗

[X-ray evaluation of renal function in children with hydronephrosis as a criterion in the selection of therapeutic tactics].

The anatomic parameters of the kidneys and the rate of glomerular filtration were measured in 77 children with unilateral hydronephrosis and in 27 children with nonobstructive diseases of the urinary tract according to the clearance of an opaque medium during excretory urography. Alterations in the anatomic parameters of the kidneys in obstructive affection did not reflect the gravity of functional disorders. It has been established that there is a possibility of carrying out a separate assessment of filtration function of the hydronephrotic and contralateral kidneys. A new diagnostic criterion is offered, namely an index of relative clearance, which enables one to measure the degree of compensatory phenomena in the preserved glomeruli and the extent of sclerotic process. It has been demonstrated that accurate measurement of the functional parameters of the affected kidney should underlie the treatment choice in children with unilateral hydronephrosis.

Adolescent↗