Microgravity as a novel environmental signal affecting Salmonella enterica serovar Typhimurium virulence. (1/27)

The effects of spaceflight on the infectious disease process have only been studied at the level of the host immune response and indicate a blunting of the immune mechanism in humans and animals. Accordingly, it is necessary to assess potential changes in microbial virulence associated with spaceflight which may impact the probability of in-flight infectious disease. In this study, we investigated the effect of altered gravitational vectors on Salmonella virulence in mice. Salmonella enterica serovar Typhimurium grown under modeled microgravity (MMG) were more virulent and were recovered in higher numbers from the murine spleen and liver following oral infection compared to organisms grown under normal gravity. Furthermore, MMG-grown salmonellae were more resistant to acid stress and macrophage killing and exhibited significant differences in protein synthesis than did normal-gravity-grown cells. Our results indicate that the environment created by simulated microgravity represents a novel environmental regulatory factor of Salmonella virulence.  (+info)

Skeletal muscle disuse induces fibre type-dependent enhancement of Na(+) channel expression. (2/27)

Slow-twitch and fast-twitch muscle fibres have specific contractile properties to respond to specific needs. Since sodium current density is higher in fast-twitch than in slow-twitch fibres, sodium channels contribute to the phenotypic feature of myofibres. Phenotype determination is not irreversible: after periods of rat hindlimb unloading (HU), a model of hypogravity, a slow-to-fast transition occurs together with atrophy in the antigravity slow-twitch soleus muscle. Using cell-attached patch-clamp and northern blot analyses, we looked at sodium channel expression in soleus muscles after 1-3 weeks of HU in rats. We found that sodium channels in fast-twitch flexor digitorum brevis muscle fibres, soleus muscle fibres and 1- to 3-week HU soleus muscle fibres showed no difference in unitary conductance, open probability and voltage-dependencies of activation, fast inactivation and slow inactivation. However, muscle disuse increased sodium current density in soleus muscle fibres 2-fold, 2.5-fold and 3-fold after 1, 2 and 3 weeks of HU, respectively. The concentration of mRNA for the skeletal muscle sodium channel alpha subunit increased 2-fold after 1 week of HU but returned to the control level after 3 weeks of HU. In contrast, the concentration of mRNA for the ubiquitous sodium channel beta(1) subunit was unchanged after 1 week and had increased by 30% after 3 weeks of HU. The tetrodotoxin sensitivity of sodium currents in 3-week HU soleus muscles and the lack of mRNA signal for the juvenile skeletal muscle sodium channel alpha subunit excluded denervation in our experiments. The observed increase in sodium current density may reduce the resistance to fatigue of antigravity muscle fibres, an effect that may contribute to muscle impairment in humans after space flight or after long immobilization.  (+info)

Control of foot trajectory in human locomotion: role of ground contact forces in simulated reduced gravity. (3/27)

We studied the changes of vertical contact forces, lower limb kinematics, and electromyographic activity (EMG) at different speeds and gravitational loads. To this end healthy subjects were asked to walk on a motorized treadmill while the percentage of body weight unloaded (body weight support, BWS) was modified in steps by means of a well-characterized unloading system. BWS was set at 0, 35, 50, 75, 95, or 100% of body weight. Walking speed was 0.7, 1.1, 2, 3, or 5 km/h. We found that changing BWS between 0 and 95% resulted in drastic changes of kinetic parameters but in limited changes of the kinematic coordination. In particular, the peak vertical contact forces decreased proportionally to BWS; at 95%-BWS they were 20-fold smaller than at 0% and were applied at the forefoot only. Also, there were considerable changes of the amplitude of EMG activity of all tested lower limb muscles and a complex re-organization of the pattern of activity of thigh muscles. By contrast, the corresponding variation of the parameters that describe shape and variability of the foot path was very limited, always <30% of the corresponding values at 0 BWS. Moreover, the planar co-variation of the elevation angles was obeyed at all speed and BWS values. Minimum variance of limb trajectory occurred at 3 km/h. At 100% BWS, subjects stepped in the air, their feet oscillating back and forth just above but never contacting the treadmill. In this case, step-to-step variability of foot path was much greater than at all other BWS levels but was restored to lower values when minimal surrogate contact forces were provided during the "stance" phase. The results did not depend on the specific instruction given to the subject. Therefore we conclude that minimal contact forces are sufficient for accurate foot trajectory control.  (+info)

Change of chloride ion channel conductance is an early event of slow-to-fast fibre type transition during unloading-induced muscle disuse. (4/27)

Disuse of postural slow-twitch muscles, as it occurs in hypogravity, induces a slow-to-fast myofibre type transition. Nothing is known about the effects of weightlessness on the resting membrane chloride conductance (gCl), which controls sarcolemma excitability and influences fibre type transition during development and adult life. Using the current-clamp method, we observed that rat hindlimb unloading (HU) for 1-3 weeks increased gCl in fibres of the slow-twitch soleus (Sol) muscle toward values found in fast muscle. Northern blot analysis suggested that this effect resulted from an increased ClC-1 chloride channel mRNA level. In the meantime, a 4-fold increase in fibres expressing fast isoforms of the myosin heavy chain (MHC) was observed by immunostaining of muscle sections. Also, Sol muscle function evolved toward a fast phenotype during HU, as demonstrated by the positive shift of the threshold potential for contraction. After 3-days HU, Sol muscle immunostaining and RT-PCR experiments revealed no change in MHC protein and mRNA expression, whereas the gCl was already maximally increased, due to a pharmacologically probed, increased activity of ClC-1 channels. Thus the increase in gCl is an early event in Sol muscle experiencing unloading, suggesting that gCl may play a role in muscle adaptation to modified use. Pharmacological modulation of ClC-1 channels may help to prevent disuse-induced muscle impairment.  (+info)

Male and female rats express similar blood pressure responses to "push-pull" gravitational stress. (5/27)

Brief exposure to -G(z) ("push") reduces eye-level blood pressure (elbp) during subsequent exposure to +G(z) ("pull"). This is called the "push-pull effect." To evaluate the influence of gender and the axis of rotation (pitch vs. roll) on the push-pull effect, 10 isoflurane-anesthetized male and 10 female Sprague-Dawley rats were restrained supine on a heated tilt board. Rats were subjected to two G profiles: a control profile consisting of rotation from 0 G(z) to 90 degrees head-up tilt (+1 G(z)) for 10 s and a push-pull profile consisting of rotation from 0 G(z) to 90 degrees head-down tilt (-1 G(z)) for 2 s immediately preceding 10 s of +1 G(z) stress. A total of 16 tilts consisting of equal numbers of control and push-pull trials and equal numbers of pitch and roll rotations were imposed by using a counterbalanced design. Gender exerted a significant effect on baseline (0 G(z)) ELBP (pressure was approximately 4 mmHg higher in females). In males and females, ELBP rose to a similar extent ( approximately 8 mmHg) during push, fell to a similar extent (approximately 18 mmHg) during control +G(z) stress, and fell to a similar extent (approximately 22 mmHg) during push-pull +G(z) stress. Altering the axis of rotation between the x-axis (roll) and the y-axis (pitch) did not influence the results. Thus males and females exhibit a push-pull effect; however, gender and axis of rotation do not appear to influence the push-pull effect in anesthetized rats subjected to tilting.  (+info)

Augmentation of the push-pull effect by terminal aortic occlusion during head-down tilt. (6/27)

Tolerance to positive vertical acceleration (Gz) gravitational stress is reduced when positive Gz stress is preceded by exposure to hypogravity, which is called the "push-pull effect." The purpose of this study was to test the hypothesis that baroreceptor reflexes contribute to the push-pull effect by augmenting the magnitude of simulated hypogravity and thereby augmenting the stimulus to the baroreceptors. We used eye-level blood pressure as a measure of the effectiveness of the blood pressure regulatory systems. The approach was to augment the magnitude of the carotid hypertension (and the hindbody hypotension) when hypogravity was simulated by head-down tilt by mechanically occluding the terminal aorta and the inferior vena cava. Sixteen anesthetized Sprague-Dawley rats were instrumented with a carotid artery catheter and a pneumatic vascular occluder cuff surrounding the terminal aorta and inferior vena cava. Animals were restrained and subjected to a control gravitational (G) profile that consisted of rotation from 0 Gz to 90 degrees head-up tilt (+1 Gz) for 10 s and a push-pull G profile consisting of rotation from 0 Gz to 90 degrees head-down tilt (-1 Gz) for 2 s immediately preceding 10 s of +1 Gz stress. An augmented push-pull G profile consisted of terminal aortic vascular occlusion during 2 s of head-down tilt followed by 10 s of +1 Gz stress. After the onset of head-up tilt, the magnitude of the fall in eye-level blood pressure from baseline was -20 +/- 1.3, -23 +/- 0.7, and -28 +/- 1.6 mmHg for the control, push-pull, and augmented push-pull conditions, respectively, with all three pairwise comparisons achieving statistically significant differences (P < 0.01). Thus augmentation of negative Gz stress with vascular occlusion increased the magnitude of the push-pull effect in anesthetized rats subjected to tilting.  (+info)

Hypotensive effect of push-pull gravitational stress occurs after autonomic blockade. (7/27)

The "push-pull" effect denotes the reduced tolerance to +Gz (hypergravity) when +Gz stress is preceded by exposure to hypogravity, i.e., fractional, zero, or negative Gz. Previous studies have implicated autonomic reflexes as a mechanism contributing to the push-pull effect. The purpose of this study was to test the hypothesis that nonautonomic mechanisms can cause a push-pull effect, by using eye-level blood pressure as a measure of G tolerance. The approach was to impose control (30 s of 30 degrees head-up tilt) and push-pull (30 s of 30 degrees head-up tilt immediately preceded by 10 s of -15 degrees headdown tilt) gravitational stress after administration of hexamethonium (10 mg/kg) to inhibit autonomic ganglionic neurotransmission in four dogs. The animals were chronically instrumented with arterial and venous catheters, an ascending aortic blood flow transducer, ventricular pacing electrodes, and atrioventicular block. The animals were paced at 75 beats/min throughout the experiment. The animals were sedated with acepromazine and lightly restrained in lateral recumbency on a tilt table. After the onset of head-up tilt, the magnitude of the fall in eye-level blood pressure from baseline was -27.6 +/- 2.3 and -37.9 +/- 2.7 mmHg for the control and push-pull trials, respectively (P < 0.05). Cardiac output fell similarly in both conditions. Thus a push-pull effect attributable to a rise in total vascular conductance occurs when autonomic function is inhibited.  (+info)

Effectiveness of intermittent -Gx gravitation in preventing deconditioning due to simulated microgravity. (8/27)

This study was designed to compare the effectiveness of daily short-duration -Gx gravity exposure in preventing adverse changes in skeletal and cardiac muscles and bone due to simulated microgravity. Tail suspension for 28 days was used to simulate microgravity-induced deconditioning effects. Daily standing (STD) at 1 G for 1, 2, or 4 h/day or centrifugation (CEN) at 1.5 or 2.6 G for 1 h/day was used to provide -Gx gravitation as a countermeasure. The results indicate that the minimum gravity exposure requirements vary greatly in different systems. Cardiac muscle is most responsive to such treatment: 1 h/day of -Gx gravitation by STD was sufficient to prevent adverse changes in myocardial contractility; bone is most resistant: 4 h/day of -Gx gravitation only partially alleviated the adverse changes in physical and mechanical properties of the femur. The responsiveness of skeletal muscle is moderate: 4 h/day of -Gx gravitation prevented mass reduction and histomorphometric changes in the soleus muscle during a 28-day simulation period. Increasing gravitational intensity to 2.6 G showed less benefit or no additional benefit in preventing adverse changes in muscle and bone. The present work suggests that system specificity in responsiveness to intermittent gravity exposure should be considered one of the prerequisites in proposing intermittent artificial gravity as a potential countermeasure.  (+info)