| 1. |
- Agvald, Per, et al.
(författare)
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Increased expired NO and roles of CO2 and endogenous NO after venous gas embolism in rabbits
- 2006
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Ingår i: European Journal of Applied Physiology. - Heidelberg, Germany : Springer Berlin/Heidelberg. - 1439-6319 .- 1439-6327. ; 97:2, s. 210-215
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Tidskriftsartikel (refereegranskat)abstract
- Venous gas embolism (VGE) is a feared complication in diving, aviation, surgery and trauma. We hypothesized that air emboli in the lung circulation might change expired nitric oxide (FeNO). A single intravenous infusion of air was given (100 mul kg(-1)) to three groups of anaesthetized mechanically ventilated rabbits: (A) one with intact NO production, (B) one with intact NO production and where end-tidal CO(2) was controlled, and (C) one with endogenous NO synthesis blockade (L: -NAME, 30 mg kg(-1)). Air infusions resulted in increased FeNO of the control group from 20 (4) [mean (SD)] ppb to a peak value of 39 (4) ppb within 5 min (P < 0.05), and FeNO was still significantly elevated [27 (2) ppb] after 20 min (P < 0.05). Parallel to the NO increase there were significant decreases in end-tidal CO(2 )(ETCO(2)) and mean arterial pressure and an increase in insufflation pressure. In group B, when CO(2) was supplemented after air infusion, NO was suppressed (P = 0.033), but was still significantly elevated compared with pre-infusion control (P < 0.05). In group C, all animals died within 40 min of air infusion whereas all animals in the other groups were still alive at this time point. We conclude that venous air embolization increases FeNO, and that a part of this effect is due to the concomitant decrease in ETCO(2). Furthermore, an intact NO production may be critical for the tolerance to VGE. Finally, FeNO might have a potential in the diagnosis and monitoring of pulmonary gas embolism.
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| 2. |
- Karlsson, Lars L., et al.
(författare)
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Venous gas emboli and exhaled nitric oxide with simulated and actual extravehicular activity
- 2009
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Ingår i: Respiratory Physiology & Neurobiology. - : Elsevier BV. - 1569-9048 .- 1878-1519. ; 169, s. S59-S62
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Tidskriftsartikel (refereegranskat)abstract
- The decompression experienced due to the change in pressure from a space vehicle (1013hPa) to that in a suit for extravehicular activity (EVA) (386hPa) was simulated using a hypobaric chamber. Previous ground-based research has indicated around a 50% occurrence of both venous gas emboli (VGE) and symptoms of decompression illness (DCI) after similar decompressions. In contrast, no DCI symptoms have been reported from past or current space activities. Twenty subjects were studied using Doppler ultrasound to detect any VGE during decompression to 386hPa, where they remained for up to 6h. Subjects were supine to simulate weightlessness. A large number of VGE were found in one subject at rest, who had a recent arm fracture; a small number of VGE were found in another subject during provocation with calf contractions. No changes in exhaled nitric oxide were found that can be related to either simulated EVA or actual EVA (studied in a parallel study on four cosmonauts). We conclude that weightlessness appears to be protective against DCI and that exhaled NO is not likely to be useful to monitor VGE.
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| 3. |
- Kos, O., et al.
(författare)
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Elevated serum soluble CD200 and CD200R as surrogate markers of bone loss under bed rest conditions
- 2014
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 60, s. 33-40
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Tidskriftsartikel (refereegranskat)abstract
- CD200 is a transmembrane protein that belongs to the immunoglobulin family of proteins and is ubiquitously expressed on a variety of cell types. Upon interaction with its receptors (CD200Rs) expressed on myeloid-derived cells and T lymphocytes, an immunoregulatory signal is delivered to receptor-expressing cells. Previous studies have implicated a role for CD200:CD200R in the regulation of the expression of mRNA markers of osteoclastogenesis/osteoblastogenesis, following interaction of CD200 (on osteoblast precursors) with CD200R1 (on osteoclast precursors). Signaling of CD200R1 is hypothesized to attenuate osteoclastogenesis. We have investigated whether levels of soluble forms of CD200 and/or CD200R1 (sCD200, sCD200R1) are altered in volunteers undergoing 6° head down tilt bed rest to mimic conditions of microgravity known to be associated with preferential osteoclastogenesis and whether countermeasures, reported to be beneficial in attenuation of bone loss under microgravity conditions, would lead to altered sCD200 and sCD200R1 levels. Our data suggest that, as predicted, sCD200 levels fall under bed rest conditions while sCD200R1 levels rise. In subjects undergoing 30-minute per day continuous centrifugation protocols, as a countermeasure to attenuate changes which may lead to bone loss, these alterations in sCD200 and sCD200R1 levels seen under conditions of bed rest were abolished or attenuated. Our results suggest that measurement of sCD200 and/or sCD200R1 may prove a useful and rapid means of monitoring subjects at risk of bone loss and/or accessing the efficacy of treatment regimes designed to counter bone loss.
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| 4. |
- Lindholm, P, et al.
(författare)
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Time components of circulatory transport from the lungs to a peripheral artery in humans
- 2006
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Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 97:1, s. 96-102
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Tidskriftsartikel (refereegranskat)abstract
- Blood gas changes occurring in the lung undergo delay and damping on their way to a peripheral artery sampling site. Knowledge of the time components of circulatory transfer is important for the understanding of respiratory control and cardiovascular reflexes in response to blood gas transients. Providing steady state with regard to V̇A/ Q̇ distribution, cardiac output and peripheral blood flow, the relationship between the time courses of small end-tidal and peripheral PO2 changes is determined by the transfer function of the interposed vascular segment. This transfer function, expressed as delay time TD and mean transit time (MTT), was measured in six well-trained subjects, allowing the calculation of arterial time-courses from end-tidal to the reverse. They were studied at rest and during four different dynamic leg exercise intensities in the supine posture. TD and MTT amounted to 15.8 ± 1.7 (mean ± SEM) and 18.3 ± 2.1 s at rest and were shortened to 7.7 ± 0.6 and 11.5 ± 1.8 s during exercise at 170 W. The shortening of TD and MTT did not appear to be simply an inverse function of cardiac output, suggesting that the shortening occurs in the central circulatory segment but not in the arm segment. © Springer-Verlag 2006.
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| 5. |
- Nilsson, Kristofer F., 1981-, et al.
(författare)
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Formation of new bioactive organic nitrites and their identification with gas chromatography-mass spectrometry and liquid chromatography coupled to nitrite reduction
- 2011
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Ingår i: Biochemical Pharmacology. - : Elsevier. - 0006-2952 .- 1356-1839 .- 1873-2968. ; 82:3, s. 248-259
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Tidskriftsartikel (refereegranskat)abstract
- Nitric oxide (NO) donors, notably organic nitrates and nitrites are used therapeutically but tolerance develops rapidly, making the use of e.g. nitroglycerin difficult. NO donation in the pulmonary vascular bed might be useful in critically ill patients. Organic nitrites are not associated with tachyphylaxis but may induce methaemoglobinemia and systemic hypotension which might hamper their use. We hypothesised that new lung-selective NO donors can be identified by utilizing exhaled NO as measure for pulmonary NO donation and systemic arterial pressure to monitor hypotension and tolerance development. Solutions of alcohols and carbohydrates were reacted with NO gas and administered to ventilated rabbits for evaluation of in vivo NO donation. Chemical characterization was made by liquid chromatography with on-line nitrite reduction (LC-NO) and by gas chromatography-mass spectrometry (GC-MS). In vivo experiments showed that the hydroxyl-containing compounds treated with NO gas yielded potent NO donors, via nitrosylation to organic nitrites. Analyses by LC-NO showed that the reaction products were able to release NO in vitro. In GC-MS the reaction products were determined to be the organic nitrites, where some are new chemical entities. Non-polar donors preferentially increased exhaled NO with less effect on systemic blood pressure whereas more polar molecules had larger effects on systemic blood pressure and less on exhaled NO. We conclude that new organic nitrites suitable for intravenous administration are produced by reacting NO gas and certain hydroxyl-containing compounds in aqueous solutions. Selectivity of different organic nitrites towards the pulmonary and systemic circulation, respectively, may be determined by molecular polarity.
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| 6. |
- Osvald, Tobias, 1989-
(författare)
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Stadens gränsplatser : Kungliga Poliskammaren och vardagens omstridda rum i Stockholm, 1776–1835
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation explores the interaction between the inhabitants of Stockholm and the constables of the Royal Police Chamber—Sweden’s first police force—during a period in the city’s history that is associated with stagnation from the perspectives of demography and economy. The aim is to understand how space was negotiated and changed over time through everyday interactions and practices. The central question is why certain places in the urban space of Stockholm were contested. The investigation is carried out through three thematic parts. Each part investigates kinds of disorder that exhibited clear elements of spatial contestation: homelessness, pub keeping, and sanitation. Each theme is explored by considering the cases that occurred in 1776–1777, 1804, and 1835. On an empirical level, the dissertation provides new information about the practices exercised in the meeting between Stockholm’s population and its agents of order. On a more abstract level, the dissertation engages critically with and adds to current theoretical perspectives on cities and spatiality. The interaction between the ideas and reality of urban space is clarified. Suggestions are made on possible approaches to studies of cities of comparable size and in a similar period.The answer to the central question—why certain places within the urban space of Stockholm were contested—is that they were border or peripheral places. At these places, the ordered city was mainly under threat and negations could occur. Rather than an unchanging city due to stagnation, a dynamic city with micro-geographies that changed in several ways is shown.The dissertation exposes previously underexplored depths of the studied time period. Households became smaller and excluded people who took to the city by “rough sleeping”. Pubs and similar drinking establishments became more distinguished from private homes and less mobile in the urban space. The flows of uncleanliness became more controlled and directed away from the public sphere of the streets. A central result is that an urban space consisting of porous boundaries and general transgressions gave way to one of hardened and more stabilized borders. Contestation and negotiations about borders moved where these were placed in Stockholm. Small, everyday geographies shifted and became more well-organized and closed. The boundaries of the city became, over time, clearer and more essential to keep. New border places arose and old ones were reshaped. By analyzing the practices of the city’s inhabitants and police force, it is apparent how an urban space became atomized.
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| 7. |
- Rittweger, Joern, et al.
(författare)
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Short-arm centrifugation as a partially effective musculoskeletal countermeasure during 5-day head-down tilt bed rest-results from the BRAG1 study
- 2015
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Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327. ; 115:6, s. 1233-1244
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Tidskriftsartikel (refereegranskat)abstract
- Human centrifugation, also called artificial gravity (AG), is proposed as a combined strategy against detrimental effects of microgravity in long-term space missions. This study scrutinized human short-arm centrifugation as countermeasure against musculoskeletal de-conditioning. Eleven healthy male subjects [mean age of 34 (SD 7) years] completed the cross-over trial, including three campaigns of -6A degrees head-down tilt bed rest (HDT) for 5 days, with preceding baseline data collection and recovery phases. Bed rest without AG was used as control condition (Ctrl), and AG with 1 g at the center of mass applied once per day for 30 min in one bout (AG(1x30)) and in 6 bouts of 5 min (AG(6x5), 3-min rest between bouts) as experimental conditions. End-points were muscle strength, vertical jump performance, and biomarkers of bone and protein metabolism. AG(6x5) was better tolerated than AG(1x30). Bone resorption markers CTX, NTX, and DPD all increased by approximately 25 % toward the end of bed rest (P < 0.001), and nitrogen balance decreased by approximately 3 g/day (P < 0.001), without any protection by AG (P > 0.4). Decreases in vertical jump height by 2.1 (SE 0.6) cm after Ctrl bed rest was prevented by either of the AG protocols (P = 0.039). The present study yielded succinct catabolic effects upon muscle and bone metabolism that were un-prevented by AG. The preservation of vertical jump performance by AG in this study is likely caused by central nervous rather than by peripheral musculoskeletal effects.
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| 8. |
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| 9. |
- Woll, Petter S, et al.
(författare)
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Myelodysplastic Syndromes Are Propagated by Rare and Distinct Human Cancer Stem Cells In Vivo.
- 2014
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Ingår i: Cancer Cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 25:6, s. 794-808
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Tidskriftsartikel (refereegranskat)abstract
- Evidence for distinct human cancer stem cells (CSCs) remains contentious and the degree to which different cancer cells contribute to propagating malignancies in patients remains unexplored. In low- to intermediate-risk myelodysplastic syndromes (MDS), we establish the existence of rare multipotent MDS stem cells (MDS-SCs), and their hierarchical relationship to lineage-restricted MDS progenitors. All identified somatically acquired genetic lesions were backtracked to distinct MDS-SCs, establishing their distinct MDS-propagating function in vivo. In isolated del(5q)-MDS, acquisition of del(5q) preceded diverse recurrent driver mutations. Sequential analysis in del(5q)-MDS revealed genetic evolution in MDS-SCs and MDS-progenitors prior to leukemic transformation. These findings provide definitive evidence for rare human MDS-SCs in vivo, with extensive implications for the targeting of the cells required and sufficient for MDS-propagation.
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