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At least 1,531 records · Page 85

Nitric oxide synthase inhibition reduces muscle inflammation and necrosis in modified muscle use

The objective of this study was to determine the role of nitric oxide in muscle inflammation, fiber necrosis, and apoptosis of inflammatory cells in vivo. The effects of nitric oxide synthase (NOS) inhibition on the concentrations of neutrophils, ED1+ and ED2+ macrophages, apoptotic inflammatory cells, and necrotic muscle fibers in rats subjected to 10 days of hindlimb unloading and 2 days of reloading were determined. Administration of NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) significantly reduced the concentrations of neutrophils, ED1+ and ED2+ macrophages, and necrotic fibers in soleus muscle relative to water-treated controls. The concentration of apoptotic inflammatory cells was also significantly lower for L-NAME-treated animals compared with water-treated controls. However, the proportion of the inflammatory cell population that was apoptotic did not differ between L-NAME-treated and control animals, suggesting that L-NAME treatment did not decrease inflammatory cell populations by increasing the frequency of apoptosis. Thus, nitric oxide or one of its intermediates promotes muscle inflammation and fiber necrosis during modified muscle use and plays no more than a minor role in the resolution of muscle inflammation by inducing apoptosis of inflammatory cells.

Non-NASA Center↗

Alteration of renal function of rats following spaceflight

Following spaceflight, changes in renal function of humans have been suggested. To assess the effects of readaptation on renal function, urine was collected from male rats ( approximately 245 g) over a 2-wk period following a 14-day spaceflight. Rats were assigned to three groups: flight animals (n = 6), flight controls (n = 6) housed in the flight cages on the ground, and vivarium controls (n = 5) housed in standard shoe box cages. Animals were placed into individual metabolic cages for urine collection. Urine output was significantly increased for 3 days following flight. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate. Creatinine excretion rate increased over the first two postflight days. Glomerular filtration rate increased immediately following spaceflight without changes in plasma creatinine, Na+, K+, or osmolality. Increased excretion of solute was thus the result of increased delivery and a decreased percent reabsorption of the filtered load. Osmolal clearance was increased immediately postflight while free water clearance was decreased. In growing rats, the diuresis after short-duration spaceflight is the result of an increase in solute excretion with an accompanying reduction in free water clearance.

STS-58 Shuttle Project↗

Comparison of soleus muscles from rats exposed to microgravity for 10 versus 14 days

The effects of two different duration space-flights on the extent of atrophy, fiber type composition, and myosin heavy chain (MHC) content of rat soleus muscles were compared. Adult male Fisher rats (n=12) were aboard flight STS-57 and exposed to 10 days of microgravity and adult ovariectomized female Spraque-Dawley rats (n=12) were aboard flight STS-62 for 14 days. Soleus muscles were bilaterally removed from the flight and control animals and frozen for subsequent analyses. Muscle wet weights, fiber types (I, IC, IIC, and IIA), cross-sectional area, and MHC content were determined. Although a significant difference was found between the soleus wet weights of the two ground-based control groups, they were similar with regard to MHC content (ca 90% MHCI and ca 10% MHCIIa) and fiber type composition. Unloading of the muscles caused slow-to-fast transformations which included a decrease in the percentage of type I fibers and MHCI, an increase in fibers classified as type IC, and the expression of two fast myosin heavy chains not found in the control rat soleus muscles (MHCIId and MHCIIb). Although the amount of atrophy (ca 26%) and the extent of slow-to-fast transformation (decrease in the percentage of MHCI from 90% to 82.5%) in the soleus muscles were similar between the two spaceflights, the percentages of the fast MHCs differed. After 14 days of spaceflight, the percentage of MHCIIa was significantly lower and the percentages of MHCIId and MHCIIb were significantly higher than the corresponding MHC content of the soleus muscles from the 10-day animals. Indeed, MHCIId became the predominant fast MHC after 14 days in space. These data suggest fast-to-faster transformations continued during the longer spaceflight.

short duration↗

Salmonella infections in the absence of the major histocompatibility complex II

We examined the pathogenesis of the facultative intracellular bacterium, Salmonella typhimurium in MHCII-/-, C2D knock-out mice, and wild-type C57BL/6J mice. The MHCII knock-out shortened the kinetics of animal death and reduced the dose of S. typhimurium needed to kill mice. We measured the physiological and cytokine responses of both mouse strains after S. typhimurium injection. Animal weight loss, spleen weights, liver weights, thymus weights, and serum corticosterone concentrations were comparable after injection with several doses of bacteria. The only physiological differences observed between the two strains were observed 3 days after injection of the highest dose of bacteria tested. Serum concentrations of tumor necrosis factor alpha, interleukin-2, and interleukin-6 increased in a dose-dependent fashion irrespective of mouse MHCII expression. Therefore, even in the absence of MHCII, mice are able to mount relatively normal physiological and immunological responses. Consistent with these normal responses, an increased percentage of MHCII-/- mice, primed with a low dose of bacteria 13 days earlier, were able to survive a lethal challenge of Salmonella compared with unprimed controls. Lastly, C2D mice had significantly higher serum interleukin-10 concentrations than C57BL/6J mice 48 h after infection with all doses of S. typhimurium. C2D macrophages also secreted significantly more IL-10 and less NO and O2- after lipopolysaccharide or phorbol ester stimulation in vitro than wild-type macrophages.

Non-NASA Center↗

Developmental changes in NMDA receptor expression in the platyfish brain

We have examined the distribution of the N-methyl-D-aspartate (NMDA) receptor in the brain of a freshwater teleost using an antibody against the R1 subunit of the receptor (NMDAR1). The primary site of localization was the nucleus olfactoretinalis (NOR), a significant gonadotropin releasing hormone (GnRH)-containing brain nucleus. The number of cells expressing NMDAR1 in this nucleus was dependent upon developmental stage, with pubescent and mature animals displaying significantly more stained cells than immature and senescent animals. This is the first reported observation of age- and maturity-related NMDA receptor association with GnRH-containing brain areas.

NASA Discipline Developmental Biology↗

Vestibular influences on autonomic cardiovascular control in humans

There is substantial evidence that anatomical connections exist between vestibular and autonomic nuclei. Animal studies have shown functional interactions between the vestibular and autonomic systems. The nature of these interactions, however, is complex and has not been fully defined. Vestibular stimulation has been consistently found to reduce blood pressure in animals. Given the potential interaction between vestibular and autonomic pathways this finding could be explained by a reduction in sympathetic activity. However, rather than sympathetic inhibition, vestibular stimulation has consistently been shown to increase sympathetic outflow in cardiac and splanchnic vascular beds in most experimental models. Several clinical observations suggest that a link between vestibular and autonomic systems may also exist in humans. However, direct evidence for vestibular/autonomic interactions in humans is sparse. Motion sickness has been found to induce forearm vasodilation and reduce baroreflex gain, and head down neck flexion induces transient forearm and calf vasoconstriction. On the other hand, studies using optokinetic stimulation have found either very small, variable, or inconsistent changes in heart rate and blood pressure, despite substantial symptoms of motion sickness. Furthermore, caloric stimulation severe enough to produce nystagmus, dizziness, and nausea had no effect on sympathetic nerve activity measured directly with microneurography. No effect was observed on heart rate, blood pressure, or plasma norepinephrine. Several factors may explain the apparent discordance of these results, but more research is needed before we can define the potential importance of vestibular input to cardiovascular regulation and orthostatic tolerance in humans.

Review↗

Effect of body repositioning after venous air embolism. An echocardiographic study

BACKGROUND: Current therapy for massive venous air embolism (VAE) may include the use of the left lateral recumbent (LLR) position, although its effectiveness has been questioned. This study used transesophageal echocardiography to evaluate the effect of body repositioning on intracardiac air and acute cardiac dimension changes. METHODS: Eighteen anesthetized dogs in the supine position received a venous air injection of 2.5 ml/kg at a rate of 5 ml/ s. After 1 min the dogs were repositioned into either the LLR, LLR 10 degrees head down (LLR-10 degrees), right lateral recumbence, or remained in the supine position. RESULTS: Repositioning after VAE resulted in relocation of intracardiac air to nondependent areas of the right heart. Peak right ventricular (RV) diameter increase and mean arterial pressure decrease were greater in the repositioned animals compared with those in the supine position (P < 0.05). Right ventricular diameter and mean arterial pressure showed an inverse correlation (r = 0.81). Peak left atrial diameter decrease was greater in the LLR and LLR-10 degrees positions compared with the supine position (P < 0.05). Repositioning did not influence peak pulmonary artery pressure increase, and no correlation was found between RV diameter and pulmonary artery pressure. All animals showed electrocardiogram and echocardiographic changes reconcilable with myocardial ischemia. CONCLUSIONS: In dogs, body repositioning after VAE provided no benefit in hemodynamic performance or cardiac dimension changes, although relocation of intracardiac air was demonstrated. Right ventricular air did not appear to result in significant RV outflow obstruction, as pulmonary artery pressure increased uniformly in all groups and was not influenced by the relocation of intracardiac air. The combination of increased RV afterload and arterial hypotension, possibly with subsequent RV ischemia rather than RV outflow obstruction by an airlock appeared to be the primary mechanism for cardiac dysfunction after VAE.

NASA Discipline Environmental Health↗

Adaptation of primate vestibuloocular reflex to altered peripheral vestibular inputs. II Spatiotemporal properties of the adapted slow-phase eye velocity

1. The ability of the vestibuloocular reflex (VOR) to undergo adaptive modification after selective changes in the peripheral vestibular system was investigated in rhesus monkeys by recording three-dimensional eye movements before and after inactivation of selective semicircular canals. In the preceding paper we showed that the horizontal VOR gain evoked by passive yaw oscillations after lateral semicircular canal inactivation recovers gradually over time in a frequency-specific manner. Here we present the spatial tuning of the adapted slow-phase eye velocity and describe its spatiotemporal properties as a function of time after canal inactivation. 2. The spatial organization of the VOR was investigated during oscillations at different head positions in the pitch, roll, and yaw planes, as well as in the right anterior/left posterior and left anterior/right posterior canal planes. Acutely after bilateral inactivation of the lateral semicircular canals, a small horizontal response could still be elicited that peaked during rotations in pitched head positions that would maximally stimulate vertical semicircular canals. In addition, the phase of horizontal slow-phase velocity abruptly reversed through 180 degrees at positions close to upright, similarly to torsional slow-phase velocity. These spatial response properties suggest that the small, residual horizontal response components that are present acutely after plugging of both lateral canals originate from vertical semicircular canal signals. 3. As the horizontal response amplitude increased over time, consistent changes were also observed in the spatiotemporal tuning of horizontal slow-phase velocity. 1) The spatiotemporal response properties of horizontal slow-phase velocity acquired noncosine tuning characteristics, primarily in the pitch plane, in the right anterior/left posterior and left anterior/right posterior canal planes. Accordingly, horizontal response amplitude was nonzero during rotation in any head position in these planes and response phase varied significantly as a function of head orientation. 2) The peak horizontal response amplitude shifted spatially over time, such that 5-10 mo after plugging it was maximal during rotations at head positions close to upright. 4. In parallel to these unique spatiotemporal response properties characterizing the adapted horizontal VOR, torsional slow-phase velocity also exhibited small spatiotemporal changes after lateral canal inactivation that tended to precede in time the changes associated with the horizontal response components. In contrast, vertical slow-phase velocity in the plugged animals was unaltered and continued to be characterized by cosine-tuned spatial properties in three dimensions. 5. Recovery of the horizontal response gain during yaw oscillations in upright position, as well as the unique, noncosine spatiotemporal characteristics of the adapted horizontal VOR, were also observed in an animal with all but one vertical semicircular canals inactivated. There was, however, no sign of VOR gain recovery up to 2 mo after all semicircular canals were inactivated. These results suggest that the observed recovery of horizontal VOR is at least partly due to signals originating from the remaining intact vertical canal(s). Even in the presence of a single intact vertical canal, the improvement in horizontal gaze stability is at least partly restored through spatiotemporal changes in the processing of vestibuloocular signals that improve the gain and spatial tuning of horizontal VOR at the expense of temporal response properties.

NASA Discipline Number 16-10↗

Quantitative changes of GABA-immunoreactive cells in the hindlimb representation of the rat somatosensory cortex after 14-day hindlimb unloading by tail suspension

The present study was aimed at evaluating quantitatively gamma-aminobutyric acid (GABA) immunoreactivity in the hindlimb representation of the rat somatosensory cortex after 14 days of hindlimb unloading by tail suspension. A reduction in the number of GABA-immunoreactive cells with respect to the control animals was observed in layer Va and Vb. GABA-containing terminals were also reduced in the same layers, particularly those terminals surrounding the soma and apical dendrites of pyramidal cells in layer Vb. On the basis of previous morphological and behavioral studies of the neuromuscular system of hindlimb-suspended animals, it is suggested that the unloading due to hindlimb suspension alters afferent signaling and feedback information from intramuscular receptors to the cerebral cortex due to modifications in the reflex organization of hindlimb muscle groups. We propose that the reduction in immunoreactivity of local circuit GABAergic neurons and terminals is an expression of changes in their modulatory activity to compensate for the alterations in the afferent information.

Non-NASA Center↗

Pyridoxine deficiency affects biomechanical properties of chick tibial bone

The mechanical integrity of bone is dependent on the bone matrix, which is believed to account for the plastic deformation of the tissue, and the mineral, which is believed to account for the elastic deformation. The validity of this model is shown in this study based on analysis of the bones of vitamin B6-deficient and vitamin B6-replete chick bones. In this model, when B6-deficient and control animals are compared, vitamin B6 deficiency has no effect on the mineral content or composition of cortical bone as measured by ash weight (63 +/- 6 vs. 58 +/- 3); mineral to matrix ratio of the FTIR spectra (4.2 +/- 0.6 vs. 4.5 +/- 0.2), line-broadening analyses of the X-ray diffraction 002 peak (beta 002 = 0.50 +/- 0.1 vs. 0.49 +/- 0.01), or other features of the infrared spectra. In contrast, collagen was significantly more extractable from vitamin B6-deficient chick bones (20 +/- 2% of total hydroxyproline extracted vs. 10 +/- 3% p < or = 0.001). The B6-deficient bones also contained an increased amount of the reducible cross-links DHLNL, dehydro-dihydroxylysinonorleucine, (1.03 +/- 0.07 vs. 0.84 +/- 0.13 p < or = 0.001); and a nonsignificant increase in HLNL, dehydro-hydroxylysinonorleucine, (0.51 +/- 0.03 vs. 0.43 +/- 0.03, p < or = 0.10). There were no significant changes in bone length, bone diameter, or area moment of inertia. In four-point bending, no significant changes in elastic modulus, stiffness, offset yield deflection, or fracture deflection were detected. However, fracture load in the B6-deficient animals was decreased from 203 +/- 35 MPa to 151 +/- 23 MPa, p < or = 0.01, and offset yield load was decreased from 165 +/- 9 MPa to 125 +/- 14 MPa, p < or = 0.05. Since earlier histomorphometric studies had demonstrated that the B6-deficient bones were osteopenic, these data suggest that although proper cortical bone mineralization occurred, the alterations of the collagen resulted in changes to bone mechanical performance.

Non-NASA Center↗

Three-dimensional organization of otolith-ocular reflexes in rhesus monkeys. II. Inertial detection of angular velocity

1. The dynamic contribution of otolith signals to three-dimensional angular vestibuloocular reflex (VOR) was studied during off-vertical axis rotations in rhesus monkeys. In an attempt to separate response components to head velocity from those to head position relative to gravity during low-frequency sinusoidal oscillations, large oscillation amplitudes were chosen such that peak-to-peak head displacements exceeded 360 degrees. Because the waveforms of head position and velocity differed in shape and frequency content, the particular head position and angular velocity sensitivity of otolith-ocular responses could be independently assessed. 2. During both constant velocity rotation and low-frequency sinusoidal oscillations, the otolith system generated two different types of oculomotor responses: 1) modulation of three-dimensional eye position and/or eye velocity as a function of head position relative to gravity, as presented in the preceding paper, and 2) slow-phase eye velocity as a function of head angular velocity. These two types of otolith-ocular responses have been analyzed separately. In this paper we focus on the angular velocity responses of the otolith system. 3. During constant velocity off-vertical axis rotations, a steady-state nystagmus was elicited that was maintained throughout rotation. During low-frequency sinusoidal off-vertical axis oscillations, dynamic otolith stimulation resulted primarily in a reduction of phase leads that characterize low-frequency VOR during earth-vertical axis rotations. Both of these effects are the result of an internally generated head angular velocity signal of otolithic origin that is coupled through a low-pass filter to the VOR. No change in either VOR gain or phase was observed at stimulus frequencies larger than 0.1 Hz. 4. The dynamic otolith contribution to low-frequency angular VOR exhibited three-dimensional response characteristics with some quantitative differences in the different response components. For horizontal VOR, the amplitude of the steady-state slow-phase velocity during constant velocity rotation and the reduction of phase leads during sinusoidal oscillation were relatively independent of tilt angle (for angles larger than approximately 10 degrees). For vertical and torsional VOR, the amplitude of steady-state slow-phase eye velocity during constant velocity rotation increased, and the phase leads during sinusoidal oscillation decreased with increasing tilt angle. The largest steady-state response amplitudes and smallest phase leads were observed during vertical/torsional VOR about an earth-horizontal axis. 5. The dynamic range of otolith-borne head angular velocity information in the VOR was limited to velocities up to approximately 110 degrees/s. Higher head velocities resulted in saturation and a decrease in the amplitude of the steady-state response components during constant velocity rotation and in increased phase leads during sinusoidal oscillations. 6. The response characteristics of otolith-borne angular VORs were also studied in animals after selective semicircular canal inactivation. Otolith angular VORs exhibited clear low-pass filtered properties with a corner frequency of approximately 0.05-0.1 Hz. Vectorial summation of canal VOR alone (elicited during earth-vertical axis rotations) and otolith VOR alone (elicited during off-vertical axis oscillations after semicircular canal inactivation) could not predict VOR gain and phase during off-vertical axis rotations in intact animals. This suggests a more complex interaction of semicircular canal and otolith signals. 7. The results of this study show that the primate low-frequency enhancement of VOR dynamics during off-vertical axis rotation is independent of a simultaneous activation of the vertical and torsional "tilt" otolith-ocular reflexes that have been characterized in the preceding paper. (ABSTRACT TRUNCATED).

NASA Discipline Neuroscience↗

Altered skeletal pattern of gene expression in response to spaceflight and hindlimb elevation

Spaceflight leads to osteopenia, in part by inhibiting bone formation. Using an animal model (hindlimb elevation) that simulates the weightlessness of spaceflight, we and others showed a reversible inhibition of bone formation and bone mineralization. In this study, we have measured the mRNA levels of insulin-like growth factor I (IGF-I), IGF-I receptor (IGF-IR), alkaline phosphatase, and osteocalcin in the tibiae of rats flown aboard National Aeronautics and Space Administration Shuttle Flight STS-54 and compared the results with those obtained from their ground-based controls and from the bones of hindlimb-elevated animals. Spaceflight and hindlimb elevation transiently increase the mRNA levels for IGF-I, IGF-IR, and alkaline phosphatase but decrease the mRNA levels for osteocalcin. The changes in osteocalcin and alkaline phosphatase mRNA levels are consistent with a shift toward decreased maturation, whereas the rise in IGF-I and IGF-IR mRNA levels may indicate a compensatory response to the fall in bone formation. We conclude that skeletal unloading during spaceflight or hindlimb elevation resets the pattern of gene expression in the osteoblast, giving it a less mature profile.

NASA Discipline Musculoskeletal↗

Skeletal unloading induces resistance to insulin-like growth factor I

In previous studies with a hindlimb elevation model, we demonstrated that skeletal unloading transiently inhibits bone formation. This effect is limited to the unloaded bones (the normally loaded humerus does not cease growing), suggesting that local factors are of prime importance. IGF-I is one such factor; it is produced in bone and stimulates bone formation. To determine the impact of skeletal unloading on IGF-I production and function, we assessed the mRNA levels of IGF-I and its receptor (IGF-IR) in the proximal tibia and distal femur of growing rats during 2 weeks of hindlimb elevation. The mRNA levels for IGF-I and IGF-IR rose during hindlimb elevation, returning toward control values during recovery. This was accompanied by a 77% increase in IGF-I levels in the bone, peaking at day 10 of unloading. Changes in IGF binding protein levels were not observed. Infusion of IGF-I (200 micrograms/day) during 1 week of hindlimb elevation doubled the increase in bone mass of the control animals but failed to reverse the cessation of bone growth in the hindlimb-elevated animals. We conclude that skeletal unloading induces resistance to IGF-I, which may result secondarily in increased local production of IGF-I.

NASA Center ARC↗

Influence of suspension on the oxidative burst by rat neutrophils

The influence of spaceflight on the oxidative burst of neutrophils is not known. The present study was designed to evaluate the influence of antiorthostatic suspension, a ground-based modeling system designed to simulate certain aspects of weightlessness that occur after spaceflight, on the capacity of rat neutrophils to express the oxidative burst, an important host defense mechanism against microbial pathogens. Rats were suspended in whole body harnesses in the antiorthostatic orientation for a 3- or 7-day period. Control rats were suspended orthostatically or allowed to remain in vivarium cages without the attachment of any suspension materials. After suspension, peripheral blood was harvested and neutrophils were isolated by density gradient centrifugation. The enriched neutrophil preparations were stimulated with N-formyl-methionyl-leucine-phenylalanine and phorbol myristic acid to induce the oxidative burst. It was found that neutrophils isolated from suspended animals released the same levels of superoxide anion as did vivarium control animals that were not suspended, indicating that whole body suspension did not alter this aspect of rat neutrophil function.

Non-NASA Center↗

Substrate oxidation capacity in rodent skeletal muscle: effects of exposure to zero gravity

A study was conducted, as part of the integrated National Aeronautics and Space Administration Space Life Sciences 1 mission flown in June of 1991, to ascertain the effects of 9 days of exposure to zero gravity on the capacity of rodent skeletal muscle fiber types to oxidize either [14C]pyruvate or [14C]palmitate under state 3 metabolic conditions, i.e., nonlimiting amounts of substrate and cofactors. In addition, activity levels of marker enzymes of the tricarboxylic acid cycle, malate shuttle, and beta-oxidation were measured. Results showed that significant differences in muscle weight occurred in both the predominantly slow vastus intermedius and predominantly fast vastus lateralis of flight vs. control groups (P < 0.05). Total protein content of the muscle samples was similar between groups. Both pyruvate oxidation capacity and the marker oxidative enzymes were not altered in the flight relative to control animals. However, the capacity to oxidize long-chain fatty acids was significantly reduced by 37% in both the high- and low-oxidative regions of the vastus muscle (P < 0.05). Although these findings of a selective reduction in fatty acid oxidation capacity in response to spaceflight are surprising, they are consistent with previous findings showing 1) an increased capacity to take up glucose and upregulate glucose transporter proteins and 2) a marked accumulation of triglycerides in the skeletal muscles of rats subjected to states of unloading. Thus, skeletal muscle of animals exposed to non-weight-bearing environments undergo subcellular transformations that may preferentially bias energy utilization to carbohydrates.

NASA Discipline Musculoskeletal↗

Overview of spaceflight immunology studies

The effects of spaceflight and analogues of spaceflight are discussed here and in nine accompanying articles. In this summary we present spaceflight studies with human subjects, animal subjects, and cell cultures and we review ground-based systems used to model the observed effects of spaceflight on the immune system. Human paradigms include bed rest, academic or psychological stress, physical stress, hypobaric or high altitude stress, and confinement. Animal models include antiorthostatic and orthostatic suspension, hypobarism, and confinement. The ten manuscripts in this collection were selected to provide a summary that should give the reader an overview of the various activities of spaceflight immunology researchers throughout the history of space travel. This manuscript identifies the major contributors to the study of spaceflight immunology, explains what types of studies have been conducted, and how they have changed over the years. Also presented is a discussion of the unusual limitations associated with spaceflight research and the efforts to develop appropriate ground-based surrogate model systems. Specific details, data, and mechanistic speculations will be held to a minimum, because they will be discussed in depth in the other articles in the collection.

NASA Discipline Number 18-10↗

The chronic infusion of nicotine into the developing chick embryo does not alter the density of (-)-[3H]nicotine-binding sites or vestibular function

(-)-Nicotine (1.2 mg/day) or saline was infused into chick embryos (Gallus domesticus) for 10 days beginning 12 h beyond the eight day of incubation (E8 + 12 h). Twelve h beyond the eighteenth day of incubation (E18 + 12 h), the eggs were opened to access the embryos and subcutaneous skull electrodes placed. Short latency vestibular response thresholds and input/output functions were determined to assess neurophysiological consequences of chronic nicotine administration. Samples of serum and extraembryonic (amniotic and albumen) fluid were analyzed by gas chromatography-mass spectrometry to determine the levels of nicotine and its major metabolite, cotinine. The brains were removed and divided into diencephalon and mesencephalon and the density of (-)-[3H]nicotine binding sites in each brain area was measured. Nicotine and cotinine were found in the serum and extraembryonic fluid, but nicotinic receptors were not up-regulated in the brains of animals infused with nicotine in comparison to controls. Vestibular response thresholds also did not differ between nicotine-treated and control animals.

NASA Discipline Neuroscience↗

Distribution of iodine into blood components of the Sprague-Dawley rat differs with the chemical form administered

It has been reported previously that radioactivity derived from iodine distributes differently in the Sprague-Dawley rat depending on the chemical form administered (Thrall and Bull, 1990). In the present communication we report the differential distribution of radioactivity derived from iodine (I2) and iodide (I-) into blood components. Twice as much radioiodine is in the form of I- in the plasma of animals treated with 125I- compared to 125I2-treated rats. No I2 could be detected in the plasma. With an increase in dose, increasing amounts of radioactivity derived from 125I2-treated animals distribute to whole blood compared to equivalent doses of 125I-, reaching a maxima at a dose of 15.8 mumol I/kg body weight. Most of the radioactivity derived from I2 associates with serum proteins and lipids, in particular with albumin and cholesteryl iodide. These data indicate a differential distribution of radioactivity depending on whether it is administered as iodide or iodine. This is inconsistent with the commonly held view that iodine (I2) is reduced to iodide (I-) before it is absorbed systemically from the gastrointestinal tract.

Non-NASA Center↗