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  • 51.
    Rohini Rajan, Meenu
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten.
    Unraveling Mechanisms of Insulin Resistance in Type 2 Diabetes in Human Adipocytes: Role of extracellular signal regulated kinase 1/2 (ERK1/2) and forkhead box protein 01 (FOX01)2016Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Type 2 Diabetes is characterized by hyperglycemia primarily caused due to insulin resistance in insulin responsive tissues and insufficient production of insulin by the β-cells. Insulin resistance appears to develop first in the expanding adipose tissue during caloric surplus and affects other tissues like liver and muscle by ectopic fat accumulation. In spite of significant research in field of insulin signaling, very little has been known about the mechanisms that lead to insulin resistance and T2D.

    We aim for network-wide knowledge of insulin signaling in human adipocytes and to identify mechanisms that can induce insulin resistance in diabetic individuals. We have herein focused on the transcriptional control of insulin via ERK and FOXO1, and have used mathematical modelling to gain a systems-level understanding of insulin signaling network.

    Through the work in this thesis, we present for the first time a dynamic comprehensive model for insulin signaling for the adipocytes, for both metabolic and transcriptional control, and that can simulate data from both normal and diabetic individuals. We described insulin regulation of ERK phosphorylation and showed that both its insulin sensitivity and maxima  response to insulin was curtailed in adipocytes from diabetic individuals (Paper I). Our findings indicate that insulin regulated ERK pathway exerts control on transcription not only through phosphorylation of Elk-1 but also through phosphorylation of FOXO1 and exerts translational control via phosphorylation of ribosomal protein S6 (Paper I, II). Furthermore, we showed that insulin-induced FOXO1 phosphorylation or its insulin sensitivity was not impaired in diabetic individuals, although FOXO1 protein level was reduced by 45% in adipocytes from patients with type 2 diabetes. Comprehensive analysis of the detailed insulin signaling model showed that attenuation of the feedback from mTORC1 to IRS1-Ser307 explained dominant part of the insulin resistance seen in adipocytes from diabetic individuals (Paper II). More interestingly, inhibition of FOXO1 with a dominant negative construct of FOXO1, mimicked the diabetic state in the adipocytes, with the similarity extending to both insulin signaling as well as the reduced protein levels, as seen in the diabetic adipocytes. We also show that mTORC1 and FOXO1 maintain each other’s expression/activity in the human adipocytes (Paper II, III). Our findings thus demonstrate that the interplay between mTORC1 and FOXO1 maintains normal insulin signaling in the human adipocytes.

    Delarbeten
    1. A Single Mechanism Can Explain Network-wide Insulin Resistance in Adipocytes from Obese Patients with Type 2 Diabetes
    Öppna denna publikation i ny flik eller fönster >>A Single Mechanism Can Explain Network-wide Insulin Resistance in Adipocytes from Obese Patients with Type 2 Diabetes
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    2014 (Engelska)Ingår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 289, nr 48, s. 33215-33230Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The response to insulin is impaired in type 2 diabetes. Much information is available about insulin signaling, but understanding of the cellular mechanisms causing impaired signaling and insulin resistance is hampered by fragmented data, mainly obtained from different cell lines and animals. We have collected quantitative and systems-wide dynamic data on insulin signaling in primary adipocytes and compared cells isolated from healthy and diabetic individuals. Mathematical modeling and experimental verification identified mechanisms of insulin control of the MAPKs ERK1/2. We found that in human adipocytes, insulin stimulates phosphorylation of the ribosomal protein S6 and hence protein synthesis about equally via ERK1/2 and mTORC1. Using mathematical modeling, we examined the signaling network as a whole and show that a single mechanism can explain the insulin resistance of type 2 diabetes throughout the network, involving signaling both through IRS1, PKB, and mTOR and via ERK1/2 to the nuclear transcription factor Elk1. The most important part of the insulin resistance mechanism is an attenuated feedback from the protein kinase mTORC1 to IRS1, which spreads signal attenuation to all parts of the insulin signaling network. Experimental inhibition of mTORC1 using rapamycin in adipocytes from non-diabetic individuals induced and thus confirmed the predicted network-wide insulin resistance.

    Ort, förlag, år, upplaga, sidor
    American Society for Biochemistry and Molecular Biology, 2014
    Nationell ämneskategori
    Klinisk medicin
    Identifikatorer
    urn:nbn:se:liu:diva-113198 (URN)10.1074/jbc.M114.608927 (DOI)000345636600015 ()25320095 (PubMedID)
    Anmärkning

    Funding Agencies|Swedish Diabetes Fund; University of Linkoping; Swedish Research Council

    Tillgänglig från: 2015-01-13 Skapad: 2015-01-12 Senast uppdaterad: 2017-12-05
    2. Systems-wide Experimental and Modeling Analysis of Insulin Signaling through Forkhead Box Protein O1 (FOXO1) in Human Adipocytes, Normally and in Type 2 Diabetes
    Öppna denna publikation i ny flik eller fönster >>Systems-wide Experimental and Modeling Analysis of Insulin Signaling through Forkhead Box Protein O1 (FOXO1) in Human Adipocytes, Normally and in Type 2 Diabetes
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    2016 (Engelska)Ingår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 291, nr 30, s. 15806-15819Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Insulin resistance is a major aspect of type 2 diabetes (T2D), which results from impaired insulin signaling in target cells. Signaling to regulate forkhead box protein O1 (FOXO1) may be the most important mechanism for insulin to control transcription. Despite this, little is known about how insulin regulates FOXO1 and how FOXO1 may contribute to insulin resistance in adipocytes, which are the most critical cell type in the development of insulin resistance. We report a detailed mechanistic analysis of insulin control of FOXO1 in human adipocytes obtained from non-diabetic subjects and from patients with T2D. We show that FOXO1 is mainly phosphorylated through mTORC2-mediated phosphorylation of protein kinase B at Ser(473) and that this mechanism is unperturbed in T2D. We also demonstrate a cross-talk from the MAPK branch of insulin signaling to stimulate phosphorylation of FOXO1. The cellular abundance and consequently activity of FOXO1 are halved in T2D. Interestingly, inhibition of mTORC1 with rapamycin reduces the abundance of FOXO1 to the levels in T2D. This suggests that the reduction of the concentration of FOXO1 is a consequence of attenuation of mTORC1, which defines much of the diabetic state in human adipocytes. We integrate insulin control of FOXO1 in a network-wide mathematical model of insulin signaling dynamics based on compatible data from human adipocytes. The diabetic state is network-wide explained by attenuation of an mTORC1-to-insulin receptor substrate-1 (IRS1) feedback and reduced abundances of insulin receptor, GLUT4, AS160, ribosomal protein S6, and FOXO1. The model demonstrates that attenuation of the mTORC1-to-IRS1 feedback is a major mechanism of insulin resistance in the diabetic state.

    Ort, förlag, år, upplaga, sidor
    Rockville, Maryland: American Society for Biochemistry and Molecular Biology, 2016
    Nationell ämneskategori
    Endokrinologi och diabetes
    Identifikatorer
    urn:nbn:se:liu:diva-130998 (URN)10.1074/jbc.M116.715763 (DOI)000380584200033 ()27226562 (PubMedID)
    Anmärkning

    Funding agencies|Swedish Diabetes Fund, University of Linköping; Swedish Research Council; AstraZeneca

    Tillgänglig från: 2016-09-02 Skapad: 2016-09-02 Senast uppdaterad: 2019-06-28Bibliografiskt granskad
  • 52.
    Röcklinsberg, Christoph
    Linköpings universitet, Institutionen för ekonomisk och industriell utveckling, Fackspråk. Linköpings universitet, Filosofiska fakulteten.
    Der 'kulturelle Raum' als Ressource in detuschen und schwedischen Tischgesprächen2014Ingår i: Verstehen und Verständigung.: Programm und Informationen, 2014, s. 166-167Konferensbidrag (Refereegranskat)
  • 53.
    Sandberg, Olof
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Metaphyseal Fracture Healing2016Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Most of what is known about fracture healing comes from studies of shaft fractures in long bones. In contrast, patients more often have fractures closer to the ends (metaphyses). Here most bone tissue has a spongy, cancellous structure different from the compact bone of the shaft. There is an increasing awareness that metaphyseal fractures heal differently. However, the more easily studied shaft healing has usually been considered as good enough representative for fracture healing in general.

    My work shows that the biology of metaphyseal healing is more different from shaft healing than was previously known and that this has implications on the effect of various commonly prescribed drugs.

    First we studied biopsies of healing cancellous bone collected from human donors. We found that the most abundant new bone formation occurred freely in the marrow rather than on the surface of old trabeculae, as described in most literature. There was little cartilage, indicating that the dominant bone formation process is mostly membranous in nature. This is a contrast to the ample cartilage formation commonly found in the well-characterized shaft fracture models.

    Next we characterized a model that allows for mechanical quantification of regenerating cancellous bone. By contrasting this cancellous healing model with the standard shaft healing model we could demonstrate that the NSAID indomethacin, the glucocorticoid dexamethasone, and the bisphosphonate alendronate all had different effects on the mechanical quality of bone regeneration in shaft and metaphysis; while anti-inflammatory drugs strongly impaired shaft healing, metaphyseal healing was not similarly affected. Alendronate had a positive effect on both models, though the effect was strongest in the metaphyseal model. Taken together these differences shed some light as to the differences in healing biology.

    The last step (within the boundaries of this thesis) was a characterization of how healing in cortical and cancellous bone differs in terms of immune cell involvement. We could find little difference between the two bone types day 3. However, day 5 an increase in the number of granulocytes could be noted in the cancellous bone while the cortical bone had a higher number of lymphocytes.

    To conclude, this work furthers our understanding of how metaphyseal healing differs from shaft healing. It has clinical implications as it motivates an increased attention to the site of fracture while contemplating treatment. I hope this thesis can be read as an argument for increased interest in metaphyseal fracture healing.

    Delarbeten
    1. Distal radial fractures heal by direct woven bone formation
    Öppna denna publikation i ny flik eller fönster >>Distal radial fractures heal by direct woven bone formation
    2013 (Engelska)Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 84, nr 3, s. 297-300Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background Descriptions of fracture healing almost exclusively deal with shaft fractures and they often emphasize endochondral bone formation. In reality, most fractures occur in metaphyseal cancellous bone. Apart from a study of vertebral fractures, we have not found any histological description of cancellous bone healing in humans.

    Patients and methods We studied histological biopsies from the central part of 12 distal radial fractures obtained during surgery 6–28 days after the injury, using routine hematoxylin and eosin staining.

    Results New bone formation was seen in 6 cases. It was always in the form of fetal-like, disorganized woven bone. It seldom had contact with old trabeculae and appeared to have formed directly in the marrow. Cartilage was scarce or absent. The samples without bone formation showed only necrosis, scar, or old cancellous bone.

    Interpretation The histology suggests that cells in the midst of the marrow respond to the trauma by direct formation of bone, independently of trabecular surfaces.

    Ort, förlag, år, upplaga, sidor
    Informa Healthcare, 2013
    Nationell ämneskategori
    Medicin och hälsovetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-96485 (URN)10.3109/17453674.2013.792769 (DOI)000319749900012 ()
    Tillgänglig från: 2013-08-23 Skapad: 2013-08-20 Senast uppdaterad: 2017-12-06
    2. Experimental models for cancellous bone healing in the rat Comparison of drill holes and implanted screws
    Öppna denna publikation i ny flik eller fönster >>Experimental models for cancellous bone healing in the rat Comparison of drill holes and implanted screws
    2015 (Engelska)Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 86, nr 6, s. 745-750Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background and purpose - Cancellous bone appears to heal by mechanisms different from shaft fracture healing. There is a paucity of animal models for fractures in cancellous bone, especially with mechanical evaluation. One proposed model consists of a screw in the proximal tibia of rodents, evaluated by pull-out testing. We evaluated this model in rats by comparing it to the healing of empty drill holes, in order to explain its relevance for fracture healing in cancellous bone. To determine the sensitivity to external influences, we also compared the response to drugs that influence bone healing. Methods - Mechanical fixation of the screws was measured by pull-out test and related to the density of the new bone formed around similar, but radiolucent, PMMA screws. The pull-out force was also related to the bone density in drill holes at various time points, as measured by microCT. Results - The initial bone formation was similar in drill holes and around the screw, and appeared to be reflected by the pull-out force. Both models responded similarly to alendronate or teriparatide (PTH). Later, the models became different as the bone that initially filled the drill hole was resorbed to restore the bone marrow cavity, whereas on the implant surface a thin layer of bone remained, making it change gradually from a trauma-related model to an implant fixation model. Interpretation - The similar initial bone formation in the different models suggests that pull-out testing in the screw model is relevant for assessment of metaphyseal bone healing. The subsequent remodeling would not be of clinical relevance in either model.

    Ort, förlag, år, upplaga, sidor
    TAYLOR & FRANCIS LTD, 2015
    Nationell ämneskategori
    Klinisk medicin
    Identifikatorer
    urn:nbn:se:liu:diva-123812 (URN)000365484500019 ()26200395 (PubMedID)
    Anmärkning

    Funding Agencies|Swedish Research Council [2031-47-5]; AFA insurance company; EU [279239]; Linkoping University; Eli Lilly and Company

    DOI does not work: 10.3109/17453674.2015.1075705

    Tillgänglig från: 2016-01-11 Skapad: 2016-01-11 Senast uppdaterad: 2018-10-29
    3. Earlier effect of alendronate in mouse metaphyseal versus diaphyseal bone healing
    Öppna denna publikation i ny flik eller fönster >>Earlier effect of alendronate in mouse metaphyseal versus diaphyseal bone healing
    2017 (Engelska)Ingår i: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 35, nr 4, s. 793-799Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Healing of injured cancellous bone is characterized by a transient stage of rapid bone formation throughout the traumatized bone volume, often followed by similarly rapid resorption. This is different from the slower diaphyseal healing via an external callus. We, therefore, hypothesized that antiresorptive treatment might have an earlier positive effect in cancellous bone healing than in diaphyseal fractures. One hundred and twenty-three male C57bl6 mice received either an internally stabilized diaphyseal osteotomy of the femur or a screw inserted into the tibial metaphysis. The mice were randomized to daily alendronate injections (200 μg/kg/day), or control injections, and killed for mechanical testing after 14, 21, or 28 days. The hypothesis was tested by a three-way Anova (time, site, and drug). The ultimate force was increased by bisphosphonate treatment in both models. There was a significant interaction between time, site, and drug (p < 0.001) so that the full positive effect of alendronate was evident in the metaphysis at 14 days, but first after 28 days in the diaphysis. While the early effect in the metaphysis might be translated into earlier healing, the late effect in the diaphysis was due to delayed remodeling of the callus, which might have less clinical importance. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

    Ort, förlag, år, upplaga, sidor
    John Wiley & Sons, 2017
    Nyckelord
    fracture, bisphosphonate, metaphysis, cancellous bone, trabecular bone, alendronate
    Nationell ämneskategori
    Klinisk medicin Ortopedi Omvårdnad
    Identifikatorer
    urn:nbn:se:liu:diva-130921 (URN)10.1002/jor.23316 (DOI)000399728400008 ()27233101 (PubMedID)
    Forskningsfinansiär
    VetenskapsrådetLinköpings universitetLandstinget i ÖstergötlandEU, FP7, Sjunde ramprogrammet
    Anmärkning

    Funding agencies: Swedish Research Council [VR 02031-47-5]; Linkoping University; Ostergotland County Council; European Communitys Seventh Framework Programme [FP7/2007-2013]

    Tillgänglig från: 2016-08-31 Skapad: 2016-08-31 Senast uppdaterad: 2018-05-03Bibliografiskt granskad
    4. Different effects of indomethacin on healing of shaft and metaphyseal fractures
    Öppna denna publikation i ny flik eller fönster >>Different effects of indomethacin on healing of shaft and metaphyseal fractures
    2015 (Engelska)Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 86, nr 2, s. 243-247Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background and purpose - NSAIDs are commonly used in the clinic, and there is a general perception that this does not influence healing in common types of human fractures. Still, NSAIDs impair fracture healing dramatically in animal models. These models mainly pertain to fractures of cortical bone in shafts, whereas patients more often have corticocancellous fractures in metaphyses. We therefore tested the hypothesis that the effect of an NSAID is different in shaft healing and metaphyseal healing. Methods - 26 mice were given an osteotomy of their left femur with an intramedullary nail. 13 received injections of indomethacin, 1 mg/kg twice daily. After 17 days of healing, the femurs were analyzed with 3-point bending and microCT. 24 other mice had holes drilled in both proximal tibias, to mimic a stable metaphyseal injury. A screw was inserted in the right tibial hole only. After 7 days of indomethacin injections or control injections, screw fixation was measured with mechanical pull-out testing and the side without a screw was analyzed with microCT. Results - In the shaft model, indomethacin led to a 35% decrease in force at failure (95% CI: 14-54). Callus size was reduced to a similar degree, as seen by microCT. Metaphyseal healing was less affected by indomethacin, as no effect on pull-out force could be seen (95% CI: - 27 to 17) and there was only a small drop in new bone volume inside the drill hole. The difference in the relative effect of indomethacin between the 2 models was statistically significant (p = 0.006). Interpretation - Indomethacin had a minimal effect on stable metaphyseal fractures, but greatly impaired healing of unstable shaft fractures. This could explain some of the differences found between animal models and clinical experience.

    Ort, förlag, år, upplaga, sidor
    Informa Healthcare, 2015
    Nationell ämneskategori
    Klinisk medicin
    Identifikatorer
    urn:nbn:se:liu:diva-117204 (URN)10.3109/17453674.2014.973328 (DOI)000351740100017 ()25323801 (PubMedID)
    Anmärkning

    Funding Agencies|Swedish Research Council; Linkoping University; Ostergotland County Council; King Gustaf V and Queen Victoria Freemason Foundation

    Tillgänglig från: 2015-04-22 Skapad: 2015-04-21 Senast uppdaterad: 2017-12-04
    5. Glucocorticoids inhibit shaft fracture healing but not metaphyseal bone regeneration under stable mechanical conditions
    Öppna denna publikation i ny flik eller fönster >>Glucocorticoids inhibit shaft fracture healing but not metaphyseal bone regeneration under stable mechanical conditions
    2015 (Engelska)Ingår i: BONE and JOINT RESEARCH, ISSN 2046-3758, Vol. 4, nr 10, s. 170-175Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Objectives Healing in cancellous metaphyseal bone might be different from midshaft fracture healing due to different access to mesenchymal stem cells, and because metaphyseal bone often heals without a cartilaginous phase. Inflammation plays an important role in the healing of a shaft fracture, but if metaphyseal injury is different, it is important to clarify if the role of inflammation is also different. The biology of fracture healing is also influenced by the degree of mechanical stability. It is unclear if inflammation interacts with stability-related factors.

    Methods We investigated the role of inflammation in three different models: a metaphyseal screw pull-out, a shaft fracture with unstable nailing (IM-nail) and a stable external fixation (ExFix) model. For each, half of the animals received dexamethasone to reduce inflammation, and half received control injections. Mechanical and morphometric evaluation was used.

    Results As expected, dexamethasone had a strong inhibitory effect on the healing of unstable, but also stable, shaft fractures. In contrast, dexamethasone tended to increase the mechanical strength of metaphyseal bone regenerated under stable conditions.

    Conclusions It seems that dexamethasone has different effects on metaphyseal and diaphyseal bone healing. This could be explained by the different role of inflammation at different sites of injury.

    Ort, förlag, år, upplaga, sidor
    BRITISH EDITORIAL SOC BONE JOINT SURGERY, 2015
    Nyckelord
    Bone; healing; fracture
    Nationell ämneskategori
    Biomaterialvetenskap
    Identifikatorer
    urn:nbn:se:liu:diva-123157 (URN)10.1302/2046-3758.410.2000414 (DOI)000364596200002 ()
    Anmärkning

    Funding Agencies|Swedish Research Council [VR 2009-6725]; Linkoping University; Ostergotland County Council; King Gustav V and Queen Victoria Mason Foundation; European Community [279239]

    Tillgänglig från: 2015-12-07 Skapad: 2015-12-04 Senast uppdaterad: 2016-03-15
  • 54.
    Skoog, Johan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Cardiovascular regulation in women with vasovagal syncope: With special reference to the venous system2016Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Although vasovagal syncope (VVS) is a common clinical condition the mechanisms behind VVS remain elusive. Upright posture is the major trigger of VVS and lower limb blood pooling affecting cardiac output has been proposed as a major determinant. The overall aim of this thesis was twofold. First, to develop new methodology for calculating limb venous compliance. Second, to study lower limb venous volume load and cardiovascular responses during hypovolemic circulatory stress caused by lower body negative pressure (LBNP) in healthy women and women with VVS, emphasizing compensatory mechanisms to maintain central blood volume.

    Net fluid filtration was associated with an underestimation ofvenous compliance. This could be accounted for with a correctionmodel. Further, a new venous wall model made it possible to adopt thevenous pressure-volume curve through the entire pressure range andthus provide a valid characterization of venous compliance.

    Calf blood pooling was similar between the groups and was not associated with tolerance to hypovolemic circulatory stress. Venous compliance was reduced at low venous pressures in VVS and correlated with decreased tolerance to circulatory stress. VVS women displayed attenuated sympathetic vasoconstrictor responses during graded circulatory stress, and mobilization of arm capacitance blood as well as capillary fluid absorption from extra- to intravascular space were reduced. Accordingly, more pronounced reductions in cardiac output were found in VVS. Thus, reduced compensatory mechanisms to maintain cardiac output could contribute to the pathogenesis oforthostatic VVS.

    In healthy women, rapid pooling in the lower limb was associated with higher tolerance to circulatory stress and more efficient cardiovascular responses, in part due to speed-dependent baroreflex-mediated sympathetic activation. In VVS however, rapid lower limb blood pooling was associated with lower tolerance and deficient cardiovascular responses. No speed-dependent baroreflexmediated sympathetic activation was found in VVS, indicating welldefined differences in cardiovascular regulation already in the initial responses to orthostatic stress.

    Delarbeten
    1. Calf venous compliance measured by venous occlusion plethysmography: methodological aspects.
    Öppna denna publikation i ny flik eller fönster >>Calf venous compliance measured by venous occlusion plethysmography: methodological aspects.
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    2015 (Engelska)Ingår i: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 115, nr 2, s. 245-56Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    PURPOSE: Calf venous compliance (C calf) is commonly evaluated with venous occlusion plethysmography (VOP) during a standard cuff deflation protocol. However, the technique relies on two not previously validated assumptions concerning thigh cuff pressure (P cuff) transmission and the impact of net fluid filtration (F filt) on C calf. The aim was to validate VOP in the lower limb and to develop a model to correct for F filt during VOP.

    METHODS: Strain-gauge technique was used to study calf volume changes in 15 women and 10 age-matched men. A thigh cuff was inflated to 60 mmHg for 4 and 8 min with a subsequent decrease of 1 mmHg s(-1). Intravenous pressure (P iv) was measured simultaneously. C calf was determined with the commonly used equation [Compliance = β 1 + 2β 2 × P cuff] describing the pressure-compliance relationship. A model was developed to identify and correct for F filt.

    RESULTS: Transmission of P cuff to P iv was 100 %. The decrease in P cuff correlated well with P iv reduction (r = 0.99, P < 0.001). Overall, our model showed that C calf was underestimated when F filt was not accounted for (all P < 0.01). F filt was higher in women (P < 0.01) and showed a more pronounced effect on C calf compared to men (P < 0.05). The impact of F filt was similar during 4- and 8-min VOP.

    CONCLUSIONS: P cuff is an adequate substitute for P iv in the lower limb. F filt is associated with an underestimation of C calf and differences in the effect of F filt during VOP can be accounted for with the correction model. Thus, our model seems to be a valuable tool in future studies of venous wall function.

    Nationell ämneskategori
    Klinisk medicin
    Identifikatorer
    urn:nbn:se:liu:diva-113393 (URN)10.1007/s00421-014-3009-4 (DOI)000347725800003 ()25272971 (PubMedID)
    Tillgänglig från: 2015-01-17 Skapad: 2015-01-17 Senast uppdaterad: 2017-12-05
    2. Reduced venous compliance: an important determinant for orthostatic intolerance in women with vasovagal syncope
    Öppna denna publikation i ny flik eller fönster >>Reduced venous compliance: an important determinant for orthostatic intolerance in women with vasovagal syncope
    Visa övriga...
    2016 (Engelska)Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 310, nr 3, s. R253-R261Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The influence of lower limb venous compliance on orthostatic vasovagal syncope (VVS) is uncertain. The most widespread technique to calculate venous compliance uses a nonphysiological quadratic regression equation. Our aim was therefore to construct a physiologically derived venous wall model (VWM) for calculation of calf venous compliance and to determine the effect of venous compliance on tolerance to maximal lower body negative pressure (LBNP). Venous occlusion plethysmography was used to study calf volume changes in 15 women with VVS (25.5 +/- 1.3 yr of age) and 15 controls (22.8 +/- 0.8 yr of age). The fit of the VWM and the regression equation to the experimentally induced pressure-volume curve was examined. Venous compliance was calculated as the derivative of the modeled pressure-volume relationship. Graded LBNP to presyncope was used to determine the LBNP tolerance index (LTI). The VWM displayed a better fit to the experimentally induced pressure-volume curve (P &lt; 0.0001). Calf blood pooling was similar in the groups and was not correlated to the LTI (r = 0.204, P = 0.30). Venous compliance was significantly reduced at low venous pressures in women with VVS (P = 0.042) and correlated to the LTI (r = 0.459, P = 0.014) in the low pressure range. No correlation was found between venous compliance at high venous pressures and the LTI. In conclusion, the new VWM accurately adopted the curvilinear pressure-volume curve, providing a valid characterization of venous compliance. Reduced venous compliance at low venous pressures may adversely affect mobilization of peripheral venous blood to the central circulation during hypovolemic circulatory stress in women with VVS.

    Ort, förlag, år, upplaga, sidor
    AMER PHYSIOLOGICAL SOC, 2016
    Nyckelord
    vasovagal syncope; orthostatic intolerance; venous compliance; venous capacitance
    Nationell ämneskategori
    Klinisk medicin
    Identifikatorer
    urn:nbn:se:liu:diva-125296 (URN)10.1152/ajpregu.00362.2015 (DOI)000369058900005 ()26561647 (PubMedID)
    Anmärkning

    Funding Agencies|Futurum-The Academy of Health Care; Jonkoping County Council; Medical Research Council of Southeast Sweden; Heart and Lung Foundation

    Tillgänglig från: 2016-02-24 Skapad: 2016-02-19 Senast uppdaterad: 2019-11-11
  • 55.
    Stensson, Niclas
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Smärt och rehabiliteringscentrum.
    Ghafouri, Bijar
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Smärt och rehabiliteringscentrum.
    Gerdle, Björn
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Smärt och rehabiliteringscentrum.
    Ghafouri, Nazdar
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Smärt och rehabiliteringscentrum.
    Alterations of anti-inflammatory lipids in plasma from women with chronic widespread pain - a case control study2017Ingår i: Lipids in Health and Disease, ISSN 1476-511X, E-ISSN 1476-511X, Vol. 16, artikel-id 112Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Chronic widespread pain conditions (CWP) such as the pain associated with fibromyalgia syndrome (FMS) are significant health problems with unclear aetiology. Although CWP and FMS can alter both central and peripheral pain mechanisms, there are no validated markers for such alterations. Pro-and anti-inflammatory components of the immune system such as cytokines and endogenous lipid mediators could serve as systemic markers of alterations in chronic pain. Lipid mediators associated with anti-inflammatory qualities - e.g., oleoylethanolamide (OEA), palmitoylethanolamide ( PEA), and stearoylethanolamide ( SEA) - belong to N-acylethanolamines (NAEs). Previous studies have concluded that these lipid mediators may modulate pain and inflammation via the activation of peroxisome proliferator activating receptors (PPARs) and the activation of PPARs may regulate gene transcriptional factors that control the expression of distinct cytokines. Methods: This study investigates NAEs and cytokines in 17 women with CWP and 21 healthy controls. Plasma levels of the anti-inflammatory lipids OEA, PEA, and SEA, the pro-inflammatory cytokines TNF-alpha, IL-1 beta, IL-6, and IL-8, and the anti-inflammatory cytokine IL-10 were investigated. T-test of independent samples was used for group comparisons. Bivariate correlation analyses, and multivariate regression analysis were performed between lipids, cytokines, and pain intensity of the participants. Results: Significantly higher levels of OEA and PEA in plasma were found in CWP. No alterations in the levels of cytokines existed and no correlations between levels of lipids and cytokines were found. Conclusions: We conclude that altered levels of OEA and PEA might indicate the presence of systemic inflammation in CWP. In addition, we believe our findings contribute to the understanding of the biochemical mechanisms involved in chronic musculoskeletal pain.

  • 56.
    Ström, Jakob O
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet.
    Theodorsson, Annette
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Neurokirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Neurokirurgiska kliniken US.
    Theodorsson, Elvar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Klinisk kemi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk kemi.
    Hormesis and Female Sex Hormones2011Ingår i: Pharmaceuticals, ISSN 1424-8247, E-ISSN 1424-8247, Vol. 4, s. 726-740Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hormone replacement after menopause has in recent years been the subject of intense scientific debate and public interest and has sparked intense research efforts into the biological effects of estrogens and progestagens. However, there are reasons to believe that the doses used and plasma concentrations produced in a large number of studies casts doubt on important aspects of their validity. The concept of hormesis states that a substance can have diametrically different effects depending on the concentration. Even though estrogens and progestagens have proven prone to this kind of dose-response relation in a multitude of studies, the phenomenon remains clearly underappreciated as exemplified by the fact that it is common practice to only use one hormone dose in animal experiments. If care is not taken to adjust the concentrations of estrogens and progestagens to relevant biological conditions, the significance of the results may be questionable. Our aim is to review examples of female sexual steroids demonstrating bidirectional dose-response relations and to discuss this in the perspective of hormesis. Some examples are highlighted in detail, including the effects on cerebral ischemia, inflammation, cardiovascular diseases and anxiety. Hopefully, better understanding of the hormesis phenomenon may result in improved future designs of studies of female sexual steroids.

  • 57.
    Svedin, Carl Göran
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Barn- och ungdomspsykiatriska kliniken.
    Priebe, Gisela
    Institutionen för psykologi, Lunds universitet.
    Wadsby, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Jonsson, Linda
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Barn- och ungdomspsykiatriska kliniken.
    Fredlund, Cecilia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Unga sex och Internet – i en föränderlig värld2015Rapport (Övrigt vetenskapligt)
    Abstract [sv]

    Avdelningen för barn och ungdomspsykiatri vid Linköpings universitet fick i uppdrag av Stiftelsen Allmänna Barnhuset att tillsammans med Statistiska Centralbyrån (SCB) genomföra en kvantitativ studie bland unga i gymnasieskolans år 3. Avtalets huvudfokus var att samla in kunskap om ungdomars sexualitet, erfarenheter av övergrepp, sexuell exponering, sexuell exponering via digitala medier i enlighet med Regeringsbeslut S2013/8825/FST. Inom ramen för uppdraget skulle samråd med Ungdomsstyrelsen och Folkhälsomyndigheten tas och undersökningen skulle ske i samarbete med Lunds Universitet.

    Samtidigt med detta gavs ett uppdrag från socialförvaltnings utvecklingsenhet i Stockholms stad, om en komplettering genom en vidgad datainsamling i Stockholms stad. Detta uppdrag skulle framför allt fokusera på barn och ungdomar i sexhandel/prostitution samt de som skadar sig själva med sex. Då de två studierna använt en identisk enkät och det i analyserna av materialet visat sig vara väldigt små skillnader mellan de två dataseten så redovisas i denna rapport det sammanlagda materialet.

    Detta är den tredje stora nationella studien på området om ungdomars sexualitet och utsatthet för sexuella övergrepp och sexuell exploatering. Den första studien Ungdomars sexualitet –attityder och erfarenheter (Svedin &Priebe, 2004) var ett uppdrag inom ramen för den statliga utredningen Sexuell exploatering av barn i Sverige (SOU, 2004:71). Den andra undersökningen Unga, sex och internet (Svedin & Priebe, 2009) genomfördes på uppdrag av Ungdomsstyrelsen i avsikt att genomföra en kvantitativ studie bland unga i gymnasieskolans år 3 samt bland Riksförbundet för homosexuella, bisexuella och transpersoners rättigheters (RFSL) medlemmar i relevant ålder. Dessa två studier, vars vetenskapliga publikationer presenteras i bilaga 1, har inom centrala områden använt samma enkät vilket möjliggör en jämförelse med den aktuella studien men också att studera trender över tid. Att just kunna jämföra olika undersökningar med varandra och över tid är tämligen unikt vilket ofta rekommenderas från olika håll. Samtidigt som centrala frågeområden som t.ex. sexuella övergrepp och sexuell exploatering behållits så har andra områden bytts ut. I denna rapport är områden som själskadebeteende, sex som självskadebeteende, människohandel för sexuella syften samt mobbing nya (enkäten bilaga 2).

  • 58.
    Svensson, C
    et al.
    Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US.
    Dremetsika, A
    Eriksson, P
    Zachrisson, Helene
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärt- och Medicincentrum, Fysiologiska kliniken US. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Utvidgat undersökningsprotokoll för detektion av tidig arterit2015Konferensbidrag (Refereegranskat)
  • 59.
    Tønseth, Kim Alexander
    et al.
    Oslo universitetssykehus, Rikshospitalet, Oslo, Norge.
    Bjark, Therese
    Oslo universitetssykehus, Rikshospitalet, Oslo, Norge.
    Kratz, Gunnar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Hand och plastikkirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Gross, Annika
    Oslo universitetssykehus, Rikshospitalet, Oslo, Norge.
    Kirschner, Rolf
    Oslo universitetssykehus, Rikshospitalet, Oslo, Norge.
    Schreiner, Thomas
    Oslo universitetssykehus, Rikshospitalet, Oslo, Norge.
    Diseth, Trond H.
    Oslo universitetssykehus, Rikshospitalet, Oslo, Norge.
    Haraldsen, Ira
    Oslo universitetssykehus, Rikshospitalet, Oslo, Norge.
    Kjønnskorrigerende kirurgived transseksualisme2010Ingår i: Tidsskrift for Den norske legeforening, ISSN 0029-2001, Vol. 130, nr 4, s. 376-379Artikel, forskningsöversikt (Refereegranskat)
    Abstract [no]

    Bakgrunn. Oslo universitetssykehus,Rikshospitalet har siden 1979 hattlandsfunksjon for behandling avpasienter med transseksualisme. Påårsbasis henvises 50–70 pasienter tilutredning, hvorav rundt 20 pasienterblir diagnostisert som transseksuelle.Årlig henvises omtrent 15 pasienter avdem som oppfyller kriterier for transseksualisme,og som er blitt endokrinologiskbehandlet, til kirurgisk intervensjon.I denne artikkelen beskrivesdiagnose og behandling av transseksualisme,med hovedvekt på kirurgi.Materiale og metode. Artikkelen erbasert på ikke-systematisk litteraturgjennomgangog egne kliniske og vitenskapeligeerfaringer.Resultater. Etter minimum ett årspsykiatrisk utredning og diagnostikk,og ett års påfølgende hormonellbehandling, vurderes pasientene i forholdtil kjønnskorrigerende kirurgi.Hos pasienter som konverteres framann til kvinne, vurderes brystforstørrendekirurgi hvis ikke hormonbehandlingalene har gitt tilfredsstillenderesultat. I tillegg er det aktuelt medgenital kirurgi hvor testikler og svamplegemenefjernes, og hvor neovaginaog neoklitoris konstrueres. For pasientersom konverteres fra kvinne tilmann, er det aktuelt å gjøre brystreduserendeinngrep, hysterektomi og salpingo-ooforektomi samt neopeniskonstruksjon.Ved god respons på hormonbehandlingkan klitoris rettes ut ogkonstrueres til en neopenis med ereksjonsmulighet(metoidioplastikk).Alternativt gjøres falloplastikk medbruk av lokalt vev fra lysken eller friemikrovaskulære lapper.Fortolkning. Kjønnskorrigerende kirurgived transseksualisme omfatterhovedsakelig konverterende operasjonerpå bryst og genitalia.

  • 60.
    Warntjes, Marcel
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US.
    Tisell, Anders
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US.
    Blystad, Ida
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper.
    Landtblom, A-M
    Engström, Maria
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Hälsouniversitetet.
    Lundberg, Peter
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US.
    Normalized Quantitative Magnetic Resonance Imaging on Multiple Sclerosis2013Konferensbidrag (Övrigt vetenskapligt)
  • 61.
    West, Janne
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Hälsouniversitetet.
    Blystad, Ida
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper.
    Engström, Maria
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Hälsouniversitetet.
    Warntjes, Marcel Jan Bertus
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Hälsouniversitetet. Region Östergötland, Hjärt- och Medicincentrum, Fysiologiska kliniken US.
    Lundberg, Peter
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US.
    On fully automated whole-brain tissue segementation at 1.5 T and 3 T based on quantitative MRI.2013Konferensbidrag (Övrigt vetenskapligt)
  • 62.
    Zötterman, Johan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Elmasry, Moustafa
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Olofsson, Pia
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Braskaminer kan orsaka svåra brännskador hos små barn2017Ingår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 2017, nr 19, s. 873-873Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    [No abstract available]

  • 63.
    Zötterman, Johan
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Steinvall, Ingrid
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Elmasry, Moustafa
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US. Surgery Department, Plastic Surgery Unit, Suez Canal University, Egypt.
    Better Protection of Glass-Fronted Stoves Is Needed in Sweden Because of the Increase in the Number of Contact Burns Among Small Children2018Ingår i: Journal of Burn Care & Research, ISSN 1559-047X, E-ISSN 1559-0488, Vol. 39, nr 4, s. 618-622Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The impression among the attending physicians at their Burn Centre is that the number of contact burns caused by glass-fronted stoves is increasing, particularly in the youngest group of patients. It is an interesting subgroup, as these injuries are preventable. The authors’ aim of this study was to find out whether the incidence of burns after contact with glass-fronted stoves has increased.

    The authors included all patients aged between 0 and 3.9 years who presented to the National Burn Centre during the period 2008–2015 with contact burn injuries caused by glass-fronted stoves. The change in incidence over time was calculated from national records and analyzed with simple linear regression.

    Fifty-six patients were included, of whom 20 were treated during the past 2 years of the study. Thirty-seven of the 56 were boys (66%), median (10–90 percentiles) age was 1.1 (0.7–2.5) years, percentage total body surface area burned was 0.6% (0.1–2.0), 12 were admitted for overnight stay in hospital, and seven needed operations. The incidence was 0.34/100 000 children-years during the first 2 years, and it was three times as high during the past 2 years. The increase in incidence was 0.24/100 000 children-years by each 2-year period (P = .02).

    The authors’ results indicate that contact burns among children caused by glass-fronted stoves are increasing in Sweden. The authors propose that there should be a plan for their prevention put in place.

  • 64.
    Öberg, Marie
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Region Östergötland, Sinnescentrum, Öron- näsa- och halskliniken US.
    Ingo, Elisabet
    Linköpings universitet, Institutionen för beteendevetenskap och lärande.
    On-line supportsystem för audionomer och förstagångsbrukare2017Konferensbidrag (Övrigt vetenskapligt)
  • 65.
    Öst, Anita
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Pospisilik, John Andrew
    Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
    Epigenetic modulation of metabolic decisions.2015Ingår i: Current Opinion in Cell Biology, ISSN 0955-0674, E-ISSN 1879-0410, Vol. 33, s. 88-94Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    In the recent years there has been a tremendous increase in our understanding of chromatin, transcription and the importance of metabolites in their regulation. This review highlights what is currently sparse information that suggest existence of a refined system integrating metabolic and chromatin control. We indicate possible regulatory modes, such as feed forward amplification, that may help effect and stabilize long-lasting phenotypic decisions within and even across generations using adipogenesis as the primary context.

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