ALBERT

Description: PURPOSE: The objective of this study was to evaluate drug marker absorption in relation to the gastric emptying (GE) of 0.7 mm and 3.6 mm enteric coated pellets as a function of viscosity and the underlying gastric motility. METHODS: Twelve subjects were evaluated in a 3-way crossover study. 0.7 mm caffeine and 3.6 mm acetaminophen enteric coated pellets were concurrently administered with a viscous caloric meal at the levels of 4000, 6000 and 8000 cP. Gastric motility was simultaneously measured with antral manometry and compared to time events in the plasma profiles of the drug markers. RESULTS: Caffeine, from the 0.7 mm pellets, was observed significantly earlier in the plasma than acetaminophen, from the 3.6 mm pellets, at all levels of viscosity. Motility related size differentiated GE was consistently observed at all viscosity levels, however, less variability was observed with the 4000 cP meal. Specifically, the onset of absorption from the of 3.6 mm pellets correlated with the onset of Phase II fasted state contractions (r = 0.929, p 〈 0.01). CONCLUSIONS: The timeframe of drug marker absorption and the onset of motility events were not altered within the range of viscosities evaluated. Rather, the differences in drug marker profiles from the non-digestible solids were most likely the result of the interaction between viscosity and motility influencing antral flow dynamics. The administration of the two sizes of pellets and a viscous caloric meal with subsequent monitoring of drug marker profiles is useful as a reference to assess the influence of motility patterns on the absorption profile of orally administered agents.

Description: Alteration in cytoskeletal organization appears to underlie mechanisms of gravity sensitivity in space-flown cells. Human T lymphoblastoid cells (Jurkat) were flown on the Space Shuttle to test the hypothesis that growth responsiveness is associated with microtubule anomalies and mediated by apoptosis. Cell growth was stimulated in microgravity by increasing serum concentration. After 4 and 48 h, cells filtered from medium were fixed with formalin. Post-flight, confocal microscopy revealed diffuse, shortened microtubules extending from poorly defined microtubule organizing centers (MTOCs). In comparable ground controls, discrete microtubule filaments radiated from organized MTOCs and branched toward the cell membrane. At 4 h, 30% of flown, compared to 17% of ground, cells showed DNA condensation characteristic of apoptosis. Time-dependent increase of the apoptosis-associated Fas/ APO-1 protein in static flown, but not the in-flight 1 g centrifuged or ground controls, confirmed microgravity-associated apoptosis. By 48 h, ground cultures had increased by 40%. Flown populations did not increase, though some cells were cycling and actively metabolizing glucose. We conclude that cytoskeletal alteration, growth retardation, and metabolic changes in space-flown lymphocytes are concomitant with increased apoptosis and time-dependent elevation of Fas/APO-1 protein. We suggest that reduced growth response in lymphocytes during spaceflight is linked to apoptosis.

Description: Results of the joint Russian/US studies of the effect of microgravity on bone tissues in 18 cosmonauts on return from 4.5- to 14.5-month long missions are presented. Dual-energy x-ray gamma-absorbtiometry (QDR-1000 W, Hologic, USA) was used to measure bone mineral density (BMD, g/cm2) and mineral content (BMC, g) in the whole body, the scalp including cervical vertebra, arms, ribs, sternal and lumbar regions of the spinal column, pelvis and legs. A clearly defined dependence of topography of changes upon the position of a skeletal segment in the gravity vector was established. The greatest BMD losses have been observed in the skeleton of the lower body, i.e. in pelvic bones (-11.99 +/- 1.22%), lumbar vertebra (-5.63 +/- 0.817%), and in proximal femur, particularly in the femoral neck (-8.17 +/- 1.24%). Bones of the upper skeleton were either unchanged (insignificant) or showed a positive trend. Overall changes in bone mass of the whole skeleton of male cosmonauts during the period of about 6 months on mission made up -1.41 +/- 0.406% and suggest the mean balance of calcium over flight equal to -227 +/- 62.8 mg/day. Reasoning is given to qualify these states of cosmonauts' bone tissues as local osteopenia. On the literature and results of authors' clinical evidence, discussed is availability of the densitometric data for predicting risk of trauma. A biological nature of the changes under observation is hypothesized.

Description: We studied interactions between CO2 chemoreflexes and arterial baroreflexes in 10 supine healthy young men and women. We measured vagal carotid baroreceptor-cardiac reflexes and steady-state fast Fourier transform R-R interval and photoplethysmographic arterial pressure power spectra at three arterial pressure levels (nitroprusside, saline, and phenylephrine infusions) and three end-tidal CO2 levels (3, 4, and 5%, fixed-frequency, large-tidal-volume breathing, CO2 plus O2). Our study supports three principal conclusions. First, although low levels of CO2 chemoreceptor stimulation reduce R-R intervals and R-R interval variability, statistical modeling suggests that this effect is indirect rather than direct and is mediated by reductions of arterial pressure. Second, reductions of R-R intervals during hypocapnia reflect simple shifting of vagally mediated carotid baroreflex responses on the R-R interval axis rather than changes of baroreflex gain, range, or operational point. Third, the influence of CO2 chemoreceptor stimulation on arterial pressure (and, derivatively, on R-R intervals and R-R interval variability) depends critically on baseline arterial pressure levels: chemoreceptor effects are smaller when pressure is low and larger when arterial pressure is high.

Description: Previously we reported that, after 17-day bed rest unloading of 8 humans, soleus slow fibers atrophied and exhibited increased velocity of shortening without fast myosin expression. The present ultrastructural study examined fibers from the same muscle biopsies to determine whether decreased myofilament packing density accounted for the observed speeding. Quantitation was by computer-assisted morphometry of electron micrographs. Filament densities were normalized for sarcomere length, because density depends directly on length. Thick filament density was unchanged by bed rest. Thin filaments/microm2 decreased 16-23%. Glycogen filled the I band sites vacated by filaments. The percentage decrease in thin filaments (Y) correlated significantly (P 〈 0.05) with the percentage increase in velocity (X), (Y = 0.1X + 20%, R2 = 0.62). An interpretation is that fewer filaments increases thick to thin filament spacing and causes earlier cross-bridge detachment and faster cycling. Increased velocity helps maintain power (force x velocity) as atrophy lowers force. Atrophic muscles may be prone to sarcomere reloading damage because force/microm2 was near normal, and force per thin filament increased an estimated 30%.

Description: Quantitative evaluation of gamma-aminobutyric acid immunoreactivity (GABA-IR) in the hindlimb representation of the rat somatosensory cortex after 14 days of exposure to hypergravity (hyper-G) was conducted by using computer-assisted image processing. The area of GABA-IR axosomatic terminals apposed to pyramidal cells of cortical layer V was reduced in rats exposed to hyper-G compared with control rats, which were exposed either to rotation alone or to vivarium conditions. Based on previous immunocytochemical and behavioral studies, we suggest that this reduction is due to changes in sensory feedback information from muscle receptors. Consequently, priorities for muscle recruitment are altered at the cortical level, and a new pattern of muscle activity is thus generated. It is proposed that the reduction observed in GABA-IR of the terminal area around pyramidal neurons is the immunocytochemical expression of changes in the activity of GABAergic cells that participate in reprogramming motor outputs to achieve effective movement control in response to alterations in the afferent information.

Description: Extended exposure to weightlessness results in bone loss. However, little information exists as to the precise nature or time course of this bone loss. Bone resorption results in the release of collagen breakdown products, including N-telopeptide and the pyridinium (PYD) cross-links, pyridinoline and deoxypyridinoline. Urinary pyridinoline and deoxypyridinoline are known to increase during bed rest. We assessed excretion of PYD cross-links and N-telopeptide before, during, and after long (28-day, 59-day, and 84-day) Skylab missions, as well as during short (14-day) and long (119-day) bed-rest studies. During space flight, the urinary cross-link excretion level was twice those observed before flight. Urinary excretion levels of the collagen breakdown products were also 40-50% higher, during short and long bed rest, than before. These results clearly show that the changes in bone metabolism associated with space flight involve increased resorption. The rate of response (i.e. within days to weeks) suggests that alterations in bone metabolism are an early effect of weightlessness. These studies are important for a better understanding of bone metabolism in space crews and in those who are bedridden.

Description: 64 commercial airline pilots (ages 35-64 yr, Mdn: 53) were surveyed regarding hearing loss and tinnitus. Within specific age groups, the proportions responding positively exceed the corresponding proportions in the general population reported by the National Center for Health Statistics.

Description: The development and maturation of the endolymphatic sac (ES) and duct (ED) were studied in the newt Cynops pyrrhogaster. The ES first appears as an oval capsule at the dorsal-medial tip of the otic vesicle at stage 39, about 11 days after oviposition. The ES consists of polymorphous epithelial cells with a minimum of cytoplasm. The intercellular space (IS) between the epithelial cells is narrow and has a smooth surface. At stage 44, the size of the ES increases as many vacuoles in the IS become filled. At stage 46, 18 days after oviposition, the ES elongates markedly and a slit-like lumen is found in the ES. The epithelium contains a few cell organelles which are scattered in the cytoplasm. The vacuoles in the IS are fused, which expands the IS. Two days later (stage 48), floccular material (endolymph) is present in the expanded lumen. The IS dilates and has a wide and irregular appearance. At stage 50, approximately 26 days after oviposition, the ES extends and expands significantly and crystals (otoconia) can now be seen in the widened lumen of the ES. The cytoplasm of the cuboidal epithelial cells contains an abundance of vesicles surrounded by ribosomes and Golgi complexes. Intercellular digitations are formed in the expanded IS. At stage 54, the ES forms a large bellow-like pouch. Numerous otoconia accumulate in the lumen. Free floating cells and cell debris can be seen in the lumen at this stage. The epithelial cells contain numerous cytoplasmic organelles which are evenly distributed in the cytoplasm. Granules are found in the apical and lateral cytoplasm. The IS is loose and displays a labyrinthine appearance. The primitive ED first appears as a connection between the ES and the saccule but no lumen is present inside at stage 39. At stage 46, a narrow lumen is formed in the ED, which corresponds to the formation of the ES lumen. At stage 50, as the ED extends, floccular material is seen in the lumen. At stage 54, the ED bears numerous microvilli on its luminal surface. Otoconia and endolymph are present in the ED. Tight junctions between the epithelial cells are formed at stage 46. A fully developed intercellular junctional complex is produced at stage 54. Based on the development of the ES and ED, the maturation of function of the ES and ED are discussed.

Description: An episode of nonsustained ventricular tachycardia was recorded from a crew member during the second month aboard the MIR space station. Although asymptomatic, this cardiac event increases the concern that serious cardiac dysrhythmias may be a limiting factor during long-duration spaceflight.