1,811 research outputs found

    Effects of inactivity on human muscle glutathione synthesis by a double-tracer and single-biopsy approach

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    Oxidative stress is often associated to inactivity-mediated skeletal muscle atrophy. Glutathione is one of the major antioxidant systems stimulated, both at muscular and systemic level, by activation of oxidative processes. We measured changes in glutathione availability, oxidative stress induction and the extent of atrophy mediated by 35 days of experimental bed rest in vastus lateralis muscle of healthy human volunteers. To assess muscle glutathione synthesis, we applied a novel single-biopsy and double-tracer ([2H2]glycine and [15N]glycine) approach based on evaluation of steady-state precursor incorporation in product. The correlations between the traditional (multiple-samples, one-tracer) and new (one-sample, double-tracer infusion) methods were analysed in erythrocytes by Passing–Bablok and Altman–Bland tests. Muscle glutathione absolute synthesis rate increased following bed rest from 5.5±1.1 to 11.0±1.5 mmol (kg wet tissue)−1 day−1 (mean ± s.e.m.; n =9; P =0.02) while glutathione concentration failed to change significantly. Bed rest induced vastus lateralis muscle atrophy, as assessed by pennation angle changes measured by ultrasonography (from 18.6±1.0 to 15.3±0.9 deg; P =0.01) and thickness changes (from 2.3±0.2 to 1.9±0.1 cm; P <0.001). Moreover, bed rest increased protein oxidative stress, as measured by muscle protein carbonylation changes (from 0.6±0.1 to 1.00±0.1 Oxydized-to-total protein ratio; P <0.04). In conclusion, we developed in erythrocytes a new minimally invasive method to determine peptide synthesis rate in human tissues. Application of the new method to skeletal muscle suggests that disuse atrophy is associated to oxidative stress induction aswell as to compensatory activation of the glutathione system

    EFFECTS OF PROLONGED IMMOBILIZATION ON SEQUENTIAL CHANGES IN MINERAL AND BONE DISEASE PARAMETERS

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    Bone demineralization due to immobilization was associated with transient increases in plasma/urinary Ca and a sustained PTH suppression which, in turn, induced secondary changes in plasma P and 1,25-(OH)2 vitamin D

    New Onset of Constipation during Long-Term Physical Inactivity: A Proof-of-Concept Study on the Immobility-Induced Bowel Changes

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    BackgroundThe pathophysiological mechanisms underlining constipation are incompletely understood, but prolonged bed rest is commonly considered a relevant determinant.AimsOur primary aim was to study the effect of long-term physical inactivity on determining a new onset of constipation. Secondary aim were the evaluation of changes in stool frequency, bowel function and symptoms induced by this prolonged physical inactivity.MethodsTen healthy men underwent a 7-day run-in followed by 35-day study of experimentally-controlled bed rest. The study was sponsored by the Italian Space Agency. The onset of constipation was evaluated according to Rome III criteria for functional constipation. Abdominal bloating, flatulence, pain and urgency were assessed by a 100mm Visual Analog Scales and bowel function by adjectival scales (Bristol Stool Form Scale, ease of passage of stool and sense of incomplete evacuation). Daily measurements of bowel movements was summarized on a weekly score. Pre and post bed rest Quality of Life (SF-36), general health (Goldberg's General Health) and depression mood (Zung scale) questionnaires were administered.ResultsNew onset of functional constipation fulfilling Rome III criteria was found in 60% (6/10) of participants (p=0.03). The score of flatulence significantly increased whilst the stool frequency significantly decreased during the week-by-week comparisons period (repeated-measures ANOVA, p=0.02 and p=0.001, respectively). Stool consistency and bowel symptoms were not influenced by prolonged physical inactivity. In addition, no significant changes were observed in general health, in mood state and in quality of life at the end of bed rest.ConclusionsOur results provide evidence that prolonged physical inactivity is relevant etiology in functional constipation in healthy individuals. The common clinical suggestion of early mobilization in bedridden patients is supported as well

    Effect of 21 days of horizontal bed rest on behavioural thermoregulation

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    The present study investigated the effect of 21 days of horizontal bed rest on cutaneous cold and warm sensitivity, and on behavioural temperature regulation. Healthy male subjects (N = 10) were accommodated in a hospital ward for the duration of the study and were under 24-h medical care. All activities (eating, drinking, hygiene, etc.) were conducted in the horizontal position. On the 1st and 22nd day of bed rest, cutaneous temperature sensitivity was tested by applying cold and warm stimuli of different magnitudes to the volar region of the forearm via a Peltier element thermode. Behavioural thermoregulation was assessed by having the subjects regulate the temperature of the water within a water-perfused suit (T wps) they were wearing. A control unit established a sinusoidal change in T wps, such that it varied from 27 to 42°C. The subjects could alter the direction of the change of T wps, when they perceived it as thermally uncomfortable. The magnitude of the oscillations towards the end of the trial was assumed to represent the upper and lower boundaries of the thermal comfort zone. The cutaneous threshold for detecting cold stimulus decreased (P < 0.05) from 1.6 (1.0)°C on day 1 to 1.0 (0.3)°C on day 22. No effect was observed on the ability to detect warm stimuli or on the regulated T wps. We conclude that although cold sensitivity increased after bed rest, it was not of sufficient magnitude to cause any alteration in behavioural thermoregulatory responses

    Local Intravascular Pressure Habituation in Relation to G-Induced Arm Pain

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    EIKEN O, MEKJAVIC IB, KOLEGARD R. Local intravascular pressure habituation in relation to G-induced arm pain. Aviat Space Environ Med 2012; 83:667-72. Background: During high +G(z) loads, pilots may experience arm pain. It is commonly assumed that such pain is caused by distension of blood vessels and that vascular distensibility adapts to the prevailing transmural pressure. The aim was to investigate whether vascular pressure habituation (PH) is as efficient in alleviating G-induced arm pain as using counterpressure/support garments. Methods: In Series I, 7 subjects underwent a 5-wk PH regimen, consisting of 15 40-min sessions, during which intravascular pressures in one arm were elevated by 65-105 mmHg. Before and after PH, arm pain was determined during incremental +G(z)-exposures in a centrifuge. In Series II, the effect on G-induced arm pain of wearing protective garments around the lower part of the upper arm was investigated in 10 subjects in 4 conditions: 1) counterpressure; 2) rigid support; 3) sham support; and 4) no support (control). Pain was rated using a 10-point graded scale. Results: PH reduced arm pain at 7.5 G from [median (range)] 4 (2-9) to 2 (0-5) in the pressure-habituated arm. The sham support did not affect pain compared to in the control condition (5.2; 3.0-10.0), whereas pain was reduced by both the rigid support (3.7; 1.0-8.0) and the counterpressure (2.5; 0.0-5.5). PH was as efficient in alleviating pain as the counterpressure and more efficient than the rigid support. Discussion: The results support the notion that G-induced arm pain is caused by vascular overdistension. Repeated moderate elevations of local intravascular pressure reduce G-induced arm pain, presumably because such PH reduces vascular distensibility.</p

    Methylotetracoccus oryzae Strain C50C1 Is a Novel Type Ib Gammaproteobacterial Methanotroph Adapted to Freshwater Environments

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    Methane-oxidizing microorganisms perform an important role in reducing emissions of the greenhouse gas methane to the atmosphere. To date, known bacterial methanotrophs belong to the Proteobacteria, Verrucomicrobia, and NC10 phyla. Within the Proteobacteria phylum, they can be divided into type Ia, type Ib, and type II methanotrophs. Type Ia and type II are well represented by isolates. Contrastingly, the vast majority of type Ib methanotrophs have not been able to be cultivated so far. Here, we compared the distributions of type Ib lineages in different environments. Whereas the cultivated type Ib methanotrophs (Methylococcus and Methylocaldum) are found in landfill and upland soils, lineages that are not represented by isolates are mostly dominant in freshwater environments, such as paddy fields and lake sediments. Thus, we observed a clear niche differentiation within type Ib methanotrophs. Our subsequent isolation attempts resulted in obtaining a pure culture of a novel type Ib methanotroph, tentatively named “Methylotetracoccus oryzae” C50C1. Strain C50C1 was further characterized to be an obligate methanotroph, containing C_(16:1)ω9c as the major membrane phospholipid fatty acid, which has not been found in other methanotrophs. Genome analysis of strain C50C1 showed the presence of two pmoCAB operon copies and XoxF5-type methanol dehydrogenase in addition to MxaFI. The genome also contained genes involved in nitrogen and sulfur cycling, but it remains to be demonstrated if and how these help this type Ib methanotroph to adapt to fluctuating environmental conditions in freshwater ecosystems

    Early Ib&#257;d&#803;&#299; Theology

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    Early Ib&#257;d&#803;&#299; Theology presents the critical edition of six Arabic theological texts recently discovered in two manuscripts in Mz&#257;b in Algeria dating from the middle of the 8th century. The texts were sent by their author, the prominent K&#363;fan Ib&#257;d&#803;&#299; kal&#257;m theologian ?Abd All&#257;h b. Yaz&#299;d al-Faz&#257;r&#299; to North Africa where he had a large following in the Ib&#257;d&#803;&#299; community later known as the Nukk&#257;r. They constitute the earliest extant body of Muslim kal&#257;m theology and are vital for the study of the initial development of rational theology in Islam. The sophisticated treatment of the divine attributes in these texts indicates that this subject developed considerably earlier in Islamic theology than previously accepted in modern scholarship

    Separate and combined effects of a 10-d exposure to hypoxia and inactivity on oxidative function in vivo and mitochondrial respiration ex vivo in humans

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    An integrative evaluation of oxidative metabolism was carried out in 9 healthy young men (age, 24.1 ± 1.7 yr mean ± SD) before (CTRL) and after a 10-day horizontal bed rest carried out in normoxia (N-BR) or hypoxia (H-BR, FiO2 = 0.147). H-BR was designed to simulate planetary habitats. Pulmonary O2 uptake (V̇o2) and vastus lateralis fractional O2 extraction (changes in deoxygenated hemoglobin+myoglobin concentration, Δ[deoxy(Hb+Mb)] evaluated using near-infrared spectroscopy) were evaluated in normoxia and during an incremental cycle ergometer (CE) and one-leg knee extension (KE) exercise (aimed at reducing cardiovascular constraints to oxidative function). Mitochondrial respiration was evaluated ex vivo by high-resolution respirometry in permeabilized vastus lateralis fibers. During CE V̇o2peak and Δ[deoxy(Hb+Mb)]peak were lower (P < 0.05) after both N-BR and H-BR than during CTRL; during KE the variables were lower after N-BR but not after H-BR. During CE the overshoot of Δ[deoxy(Hb+Mb)] during constant work rate exercise was greater in N-BR and H-BR than CTRL, whereas during KE a significant difference vs. CTRL was observed only after N-BR. Maximal mitochondrial respiration determined ex vivo was not affected by either intervention. In N-BR, a significant impairment of oxidative metabolism occurred downstream of central cardiovascular O2 delivery and upstream of mitochondrial function, possibly at the level of the intramuscular matching between O2 supply and utilization and peripheral O2 diffusion. Superposition of hypoxia on bed rest did not aggravate, and partially reversed, the impairment of muscle oxidative function in vivo induced by bed rest. The effects of longer exposures will have to be determined

    A novel method to allow noninvasive, longitudinal imaging of the murine immune system in vivo

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    In vivo imaging has revolutionized understanding of the spatiotemporal complexity that subserves the generation of successful effector and regulatory immune responses. Until now, invasive surgery has been required for microscopic access to lymph nodes (LNs), making repeated imaging of the same animal impractical and potentially affecting lymphocyte behavior. To allow longitudinal in vivo imaging, we conceived the novel approach of transplanting LNs into the mouse ear pinna. Transplanted LNs maintain the structural and cellular organization of conventional secondary lymphoid organs. They participate in lymphocyte recirculation and exhibit the capacity to receive and respond to local antigenic challenge. The same LN could be repeatedly imaged through time without the requirement for surgical exposure, and the dynamic behavior of the cells within the transplanted LN could be characterized. Crucially, the use of blood vessels as fiducial markers also allowed precise re-registration of the same regions for longitudinal imaging. Thus, we provide the first demonstration of a method for repeated, noninvasive, in vivo imaging of lymphocyte behavior

    Bone loss in the lower leg during 35 days of bed rest is predominantly from the cortical compartment

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    Immobilization-induced bone loss is usually greater in the epiphyses than in the diaphyses. The larger fraction of trabecular bone in the epiphyses than in the diaphyses offers an intuitive explanation to account for this phenomenon. However, recent evidence contradicts this notion and suggests that immobilizationinduced bone loss from the distal tibia epiphysis is mainly from the cortical compartment. The aim of this study was to establish whether this pattern of bone loss was a general rule during immobilization. We monitored various skeletal sites with different tissue composition during 5 weeks of immobilization. Ten healthy male volunteers with mean age of 24.3 years (SD 2.6 years) underwent strict horizontal bed rest. Bone scans were obtained during baseline data collection, at the end of bed rest and after 14 days of recovery by peripheral Quantitative Computed Tomography (pQCT). Sectional images were obtained from the distal tibia epiphysis (at 4% of the tibia's length), from the diaphysis (at 38%), from the proximal metaphysis (at 93%) and from the proximal epiphysis (at 98%), as well as from the distal femur epiphysis (at 4% of the femur's length) and from the patella. Relative bone losses were largest at the patella, where they amounted to −3.2% (SD 1.8%, pb0.001) of the baseline values, and smallest at the tibia diaphysis, where they amounted to −0.7% (SD 1.0%, p=0.019). The relative losses were generally larger from cortical than from trabecular compartments (p=0.004), and whilst all skeletal sites depicted such cortical losses, substantial trabecular losses were found only from the proximal tibia epiphysis. Results confirm that the differential losses from the various skeletal sites cannot be explained on the basis of trabecular vs. cortical tissue composition differences, but that endocortical circumference can account for the different amounts of bone loss in the tibia. The present study therefore supports the suggestion of the subendocortical layer as a transitional zone, which can readily be transformed into trabecular bone in response to immobilization. The latter will lead to cortical thinning, a factor that has been associated with the risk of fracture and with osteoarthritis
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