Research Containing: Male

Iron status and its relations with oxidative damage and bone loss during long-duration space flight on the International Space Station

by cfynanon 9 June 2015in Biology & Biotechnology No comment

BACKGROUND: Increases in stored iron and dietary intake of iron during space flight have raised concern about the risk of excess iron and oxidative damage, particularly in bone. OBJECTIVES: The objectives of this study were to perform a comprehensive assessment of iron status in men and women before, during, and after long-duration space flight and to quantify the association of iron status with oxidative damage and bone loss. DESIGN: Fasting blood and 24-h urine samples were collected from 23 crew members before, during, and after missions lasting 50 to 247 d to the International Space Station. RESULTS: Serum ferritin and body iron increased early in flight, and transferrin and transferrin receptors decreased later, which indicated that early increases in body iron stores occurred through the mobilization of iron to storage tissues. Acute phase proteins indicated no evidence of an inflammatory response during flight. Serum ferritin was positively correlated with the oxidative damage markers 8-hydroxy-2'-deoxyguanosine (r = 0.53, P < 0.001) and prostaglandin F2alpha (r = 0.26, P < 0.001), and the greater the area under the curve for ferritin during flight, the greater the decrease in bone mineral density in the total hip (P = 0.031), trochanter (P = 0.006), hip neck (P = 0.044), and pelvis (P = 0.049) after flight. CONCLUSION: Increased iron stores may be a risk factor for oxidative damage and bone resorption.

Capacity of omega-3 fatty acids or eicosapentaenoic acid to counteract weightlessness-induced bone loss by inhibiting NF-kappaB activation: from cells to bed rest to astronauts

by cfynanon 9 June 2015in Biology & Biotechnology No comment

NF-kappaB is a transcriptional activator of many genes, including some that lead to muscle atrophy and bone resorption-significant concerns for astronauts. NF-kappaB activation is inhibited by eicosapentaenoic acid (EPA), but the influence of this omega-3 fatty acid on the effects of weightlessness are unknown. We report here cellular, ground analogue, and spaceflight findings. We investigated the effects of EPA on differentiation of RAW264.7 monocyte/macrophage cells induced by receptor activator of NF-kappaB ligand (RANKL) and on activation of NF-kappaB by tumor necrosis factor alpha (TNF-alpha) or exposure to modeled weightlessness. EPA (50 microM for 24 hours) inhibited RANKL-induced differentiation and decreased activation of NF-kappaB induced by 0.2 microg/mL of TNF-alpha for 30 minutes or by modeled weightlessness for 24 hours (p < .05). In human studies, we evaluated whether NF-kappaB activation was altered after short-duration spaceflight and determined the relationship between intake of omega-3 fatty acids and markers of bone resorption during bed rest and the relationship between fish intake and bone mineral density after long-duration spaceflight. NF-kappaB was elevated in crew members after short-duration spaceflight, and higher consumption of fish (a rich source of omega-3 fatty acids) was associated with reduced loss of bone mineral density after flight (p < .05). Also supporting the cell study findings, a higher intake of omega-3 fatty acids was associated with less N-telopeptide excretion during bed rest (Pearson r = -0.62, p < .05). Together these data provide mechanistic cellular and preliminary human evidence of the potential for EPA to counteract bone loss associated with spaceflight.

Shear stress induces preimplantation embryo death that is delayed by the zona pellucida and associated with stress-activated protein kinase-mediated apoptosis

by cfynanon 9 June 2015in Biology & Biotechnology No comment

In this study, we discovered that embryos sense shear stress and sought to characterize the kinetics and the enzymatic mechanisms underlying induction of embryonic lethality by shear stress. Using a rotating wall vessel programmed to produce 1.2 dynes/cm2 shear stress, it was found that shear stress caused lethality within 12 h for E3.5 blastocysts. Embryos developed an approximate 100% increase in mitogen-activated protein kinase 8/9 (formerly known as stress-activated protein kinase/junC kinase 1/2) phosphorylation by 6 h of shear stress that further increased to approximately 350% by 12 h. Terminal deoxynucleotidyltransferase dUTP nick end labeling/apoptosis was at baseline levels at 6 h and increased to approximately 500% of baseline at 12 h, when irreversible commitment to death occurred. A mitogen-activated protein kinase 8/9 phosphorylation inhibitor, D-JNKI1, was able to inhibit over 50% of the apoptosis, suggesting a causal role for mitogen-activated protein kinase 8/9 phosphorylation in the shear stress-induced lethality. The E2.5 (compacted eight-cell/early morula stage) embryo was more sensitive to shear stress than the E3.5 (early blastocyst stage) embryo. Additionally, zona pellucida removal significantly accelerated shear stress-induced lethality while having no lethal effect on embryos in the static control. In conclusion, preimplantation embryos sense shear stress, chronic shear stress is lethal, and the zona pellucida lessens the lethal and sublethal effects of shear stress. Embryos in vivo would not experience as high a sustained velocity or shear stress as induced experimentally here. Lower shear stresses might induce sufficient mitogen-activated protein kinase 8/9 phosphorylation that would slow growth or cause premature differentiation if the zona pellucida were not intact.

Reduced heart rate variability during sleep in long-duration spaceflight

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Limited data are available to describe the regulation of heart rate (HR) during sleep in spaceflight. Sleep provides a stable supine baseline during preflight Earth recordings for comparison of heart rate variability (HRV) over a wide range of frequencies using both linear, complexity, and fractal indicators. The current study investigated the effect of long-duration spaceflight on HR and HRV during sleep in seven astronauts aboard the International Space Station up to 6 mo. Measurements included electrocardiographic waveforms from Holter monitors and simultaneous movement records from accelerometers before, during, and after the flights. HR was unchanged inflight and elevated postflight [59.6 +/- 8.9 beats per minute (bpm) compared with preflight 53.3 +/- 7.3 bpm; P < 0.01]. Compared with preflight data, HRV indicators from both time domain and power spectral analysis methods were diminished inflight from ultralow to high frequencies and partially recovered to preflight levels after landing. During inflight and at postflight, complexity and fractal properties of HR were not different from preflight properties. Slow fluctuations (<0.04 Hz) in HR presented moderate correlations with movements during sleep, partially accounting for the reduction in HRV. In summary, substantial reduction in HRV was observed with linear, but not with complexity and fractal, methods of analysis. These results suggest that periodic elements that influence regulation of HR through reflex mechanisms are altered during sleep in spaceflight but that underlying system complexity and fractal dynamics were not altered.

Effects of long-term microgravity exposure in space on circadian rhythms of heart rate variability

by cfynanon 9 June 2015in Biology & Biotechnology No comment

We evaluated their circadian rhythms using data from electrocardiographic records and examined the change in circadian period related to normal RR intervals for astronauts who completed a long-term (>/=6-month) mission in space. The examinees were seven astronauts, five men and two women, from 2009 to 2010. Their mean +/- SD age was 52.0 +/- 4.2 years (47-59 yr). Each stayed in space for more than 160 days; their average length of stay was 172.6 +/- 14.6 days (163-199 days). We conducted a 24-h Holter electrocardiography before launch (Pre), at one month after launch (DF1), at two months after launch (DF2), at two weeks before return (DF3), and at three months after landing (Post), comparing each index of frequency-domain analysis and 24-h biological rhythms of the NN intervals (normal RR intervals). Results show that the mean period of Normal Sinus (NN) intervals was within 24 +/- 4 h at each examination. Inter-individual variability differed among the stages, being significantly smaller at DF3 (Pre versus DF1 versus DF3 versus Post = 22.36 +/- 2.50 versus 25.46 +/- 4.37 versus 22.46 +/- 1.75 versus 26.16 +/- 7.18 h, p < 0.0001). The HF component increased in 2 of 7 astronauts, whereas it decreased in 3 of 7 astronauts and 1 was remained almost unchanged at DF1. During DF3, about 6 months after their stay in space, the HF component of 5 of 7 astronauts recovered from the decrease after launch, with prominent improvement to over 20% in 3 astronauts. Although autonomic nervous functions and circadian rhythms were disturbed until one month had passed in space, well-scheduled sleep and wake rhythms and meal times served as synchronizers.

An artificial testis for production of rat haploid cells

by cfynanon 9 June 2015in Biology & Biotechnology No comment

PURPOSE: We attempted to apply the microgravity cell culture system for rat testicular germ cell maturation in vitro. METHODS: Primary spermatocytes were isolated from immature male rat by sedimentation velocity. Sertoli cells were isolated from another immature male by enzyme digestions. Sertoli cell aggregates were plated into conventional tissue culture flasks and incubated at 37 degrees C for 48 hours. These pretreated Sertoli-enriched monocultures were used in preparing Sertoli cell-primary spermatocyte cocultures. And then, primary spermatocytes and Sertoli cells were cocultured in a microgravity cell culture device for 28 days. RESULTS: Cell viability rate is more than 50 % after a 28-day long period of incubation. Furthermore, about 23 % haploid germ cells are observed. CONCLUSIONS: These results using primary spermatocyte coculture with Sertoli cell aggregates under microgravity show that it is possible to mature these cells up to the round spermatid and even to elongating/elongated steps. It may be possible to overcome the male sterility due to maturation arrest at the primary spermatocyte stage.

Regulation of osteogenetic differentiation of mesenchymal stem cells by two axial rotational culture

by cfynanon 9 June 2015in Biology & Biotechnology No comment

It is crucial to understand how gravitational force affects the osteogenic differentiation of mesenchymal stem cells (MSCs), and these fundamental aspects hold promise for the development of a novel model of MSC regulation for cell proliferation and differentiation. The objective of this study was to investigate how significantly gravitational dispersion affects the spontaneously induced osteogenic differentiation of MSCs. Expression of surface antigen was measured by flow cytometry prior to two axial rotational cultures. About 12,500 hMSC cells were spread on culture wells of 1.8 cm(2) surface area and incubated for 7 days at 5% CO(2). The culture medium, 10% FCS/DMEM containing 3 ng/ml bFGF, was replaced every 3 days. Four wells then were placed in a 50-ml centrifugal tube filled with 10% FCS/DMEM without bFGF. The centrifugal tube was attached to the center of the rotor, and two axial rotational cultures were started at 10 rpm each of both rotational speeds. It was confirmed that the hMSCs used in this study expressed typical surface antigens as well as a multipotent differentiation ability for either osteogenic or adipogenic differentiation. Spontaneous expression of alkaline phosphatase (Alp) mRNA following the conventional static culture (1G condition) was suppressed by two axial rotational cultures for 7 days (p < 0.05). A separate study indicated that the cell count number eventually increased from 24,700 +/- A 6,400 to 78,400 +/- A 18,700 (p < 0.05). In addition, suppressed Alp mRNA was recovered after an additional 7-day culture under static conditions. This result indicated that dispersion of gravity is a promising modality to regulate osteogenic differentiation of hMSCs.

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Gravity and embryonic development

by cfynanon 9 June 2015in Biology & Biotechnology No comment

The relationship between the developing embryo (both plant and animal) and a gravitational field has long been contemplated. The difficulty in designing critical experiments on the surface of the earth because of its background of 1 g, has been an obstacle to a resolution of the problem. Biological responses to gravity (particularly in plants) are obvious in many cases; however, the influence of gravity as an environmental input to the developing embryo is not as obvious and has proven to be extremely difficult to define. In spite of this, over the years numerous attempts have been made using a variety of embryonic materials to come to grips with the role of gravity in development. Three research tools are available: the centrifuge, the clinostat, and the orbiting spacecraft. Experimental results are now available from all three sources. Some tenuous conclusions are drawn, and an attempt at a unifying theory on gravitational influence on embryonic development is made.

Effect of potassium citrate therapy on the risk of renal stone formation during spaceflight

by cfynanon 9 June 2015in Biology & Biotechnology No comment

PURPOSE: Exposure to microgravity affects human physiology and results in changes in urinary chemical composition during and after spaceflight, favoring an increased risk of renal stones. We assessed the efficacy of potassium citrate to decrease the stone risk during and after spaceflight. MATERIALS AND METHODS: The study was done in 30 long duration spaceflight crew members to the space stations Mir and International Space Station. Before, during and after spaceflight 24-hour urine samples were collected to assess the renal stone risk. Potassium citrate (20 mEq) was ingested daily by International Space Station crew members in a double-blind, placebo controlled study. Mir crew members performed the identical protocol but did not ingest medication. RESULTS: Potassium citrate treated crew members had decreased urinary calcium excretion and maintained the calcium oxalate supersaturation risk at preflight levels compared to that in controls. Increased urinary pH in the treatment group decreased the risk of uric acid stones. CONCLUSIONS: Results from this investigation suggest that supplementation with potassium citrate may decrease the risk of renal stone formation during and immediately after spaceflight.

Development of gravity-sensing organs in altered gravity

by cfynanon 9 June 2015in Biology & Biotechnology No comment

Experiments are described in which the development of the gravity-sensing organs was studied in newt larvae reared in microgravity on the IML-2 mission and in Aplysia embryos and larvae reared on a centrifuge at 1 to 5 g. In Aplysia embryos, the statolith (single dense mass on which gravity and linear acceleration act) was reduced in size in a graded fashion at increasing g. In early post-metamorphic Aplysia or even in isolated statocysts from such animals, the number of statoconia produced is reduced at high g. Newt larvae launched before any of the otoconia were formed and reared for 15 days in microgravity had nearly adult labyrinths at the end of the IML-2 mission. The otoliths of the saccule and utricle were the same size in flight and ground-reared larvae. However, the system of aragonitic otoconia produced in the endolymphatic sac in amphibians was much larger and developed earlier in the flight-reared larvae. At later developmental stages, the aragonitic otoconia enter and fill the saccule. One flight-reared larva was maintained for nine months post-flight and the size of the saccular otolith, as well as the volume of otoconia within the endolymphatic sac, were considerably larger than in age-matched, ground-reared newts. This suggests that rearing in microgravity initiates a process that continues for several months after introduction to 1-g, which greatly increases the volume of otoconia. The flight-reared animal had abnormal posture, pointing its head upward, whereas normal ground-reared newts always keep their head horizontal. This suggests that rearing for even a short period in microgravity can have lasting functional consequences in an animal subsequently reared in 1-g conditions on Earth.

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Research Containing: Male

Iron status and its relations with oxidative damage and bone loss during long-duration space flight on the International Space Station

Capacity of omega-3 fatty acids or eicosapentaenoic acid to counteract weightlessness-induced bone loss by inhibiting NF-kappaB activation: from cells to bed rest to astronauts

Shear stress induces preimplantation embryo death that is delayed by the zona pellucida and associated with stress-activated protein kinase-mediated apoptosis

Reduced heart rate variability during sleep in long-duration spaceflight

Effects of long-term microgravity exposure in space on circadian rhythms of heart rate variability

An artificial testis for production of rat haploid cells

Regulation of osteogenetic differentiation of mesenchymal stem cells by two axial rotational culture

Gravity and embryonic development

Effect of potassium citrate therapy on the risk of renal stone formation during spaceflight

Development of gravity-sensing organs in altered gravity