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  • 1.
    A'Roch, Roman
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Steendijk, Paul
    Oldner, Anders
    Weitzberg, Eddie
    Konrad, David
    Johansson, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Left ventricular mechanical dyssynchrony is load independent at rest and during endotoxaemia in a porcine model2009In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 196, no 4, p. 375-383Article in journal (Refereed)
    Abstract [en]

    AIM: In diseased or injured states, the left ventricle displays higher degrees of mechanical dyssynchrony. We aimed at assessing mechanical dyssynchrony ranges in health related to variation in load as well as during acute endotoxin-induced ventricular injury.

    METHODS: In 16 juvenile anaesthetized pigs, a five-segment conductance catheter was placed in the left ventricle as well as a balloon-tipped catheter in the inferior vena cava. Mechanical dyssynchrony during systole, including dyssynchrony time in per cent during systole and internal flow fraction during systole, were measured at rest and during controlled pre-load reduction sequences, as well as during 3 h of endotoxin infusion (0.25 microg kg(-)1 h(-1)).

    RESULTS: Systolic dyssynchrony and internal flow fraction did not change during the course of acute beat-to-beat pre-load alteration. Endotoxin-produced acute pulmonary hypertension by left ventricular dyssynchrony measures was not changed during the early peak of pulmonary hypertension. Endotoxin ventricular injury led to progressive increases in systolic mechanical segmental dyssynchrony (7.9 +/- 1.2-13.0 +/- 1.3%) and ventricular systolic internal flow fraction (7.1 +/- 2.4-16.6 +/- 2.8%), respectively for baseline and then at hour 3. There was no localization of dyssynchrony changes to segment or region in the ventricular long axis during endotoxin infusion.

    CONCLUSION: These results suggest that systolic mechanical dyssynchrony measures may be load independent in health and during acute global ventricular injury by endotoxin. More study is needed to validate ranges in health and disease for parameters of mechanical dyssynchrony.

  • 2. Blanchard, P. G.
    et al.
    Turcotte, V.
    Cote, M.
    Gelinas, Y.
    Nilsson, S.
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Deshaies, Y.
    Festuccia, W. T.
    Peroxisome proliferator-activated receptor activation favours selective subcutaneous lipid deposition by coordinately regulating lipoprotein lipase modulators, fatty acid transporters and lipogenic enzymes2016In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 217, no 3, p. 227-239Article in journal (Refereed)
    Abstract [en]

    Aim: Peroxisome proliferator-activated receptor (PPAR) γ activation is associated with preferential lipoprotein lipase (LPL)-mediated fatty acid storage in peripheral subcutaneous fat depots. How PPARγ agonism acts upon the multi-level modulation of depot-specific lipid storage remains incompletely understood.

    Methods: We evaluated herein triglyceride-derived lipid incorporation into adipose tissue depots, LPL mass and activity, mRNA levels and content of proteins involved in the modulation of LPL activity and fatty acid transport, and the expression/activity of enzymes defining adipose tissue lipogenic potential in rats treated with the PPARγ ligand rosiglitazone (30 mg kg−1 day−1, 23 days) after either a 10-h fasting period or a 17-h fast followed by 6 h of ad libitum refeeding.

    Results: Rosiglitazone stimulated lipid accretion in subcutaneous fat (SF) ~twofold and significantly reduced that of visceral fat (VF) to nearly half. PPARγ activation selectively increased LPL mass, activity and the expression of its chaperone LMF1 in SF. In VF, rosiglitazone had no effect on LPL activity and downregulated the mRNA levels of the transendothelial transporter GPIHBP1. Overexpression of lipid uptake and fatty acid transport proteins (FAT/CD36, FATP1 and FABP4) and stimulation of lipogenic enzyme activities (GPAT, AGPAT and DGAT) upon rosiglitazone treatment were of higher magnitude in SF.

    Conclusions: Together these findings demonstrate that the depot-specific transcriptional control of LPL induced by PPARγ activation extends to its key interacting proteins and post-translational modulators to favour subcutaneous lipid storage.

  • 3.
    Druzin, Michael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Setting neuronal chloride gradient: a new role for extracellular matrix2015In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 215, p. 45-45Article in journal (Other academic)
  • 4.
    Holmberg, Ellinor
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Johansson, Maja
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Löfgren, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Haage, David
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Allopregnanolone induces a diurnally dependent hyperphagic effect and alters feeding latency and duration in male Wistar rats2013In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 208, no 4, p. 400-409Article in journal (Refereed)
    Abstract [en]

    Aim: Gamma-aminobutyric acid (GABA)-ergic transmission from the hypothalamus is essential for normal feeding regulation, and hyperphagia can be induced by local application of GABA(A)-receptor agonists to different feeding-associated brain areas. The food intake in rats varies diurnally and that may influence the effect of GABA(A)-receptor active compounds. The progesterone metabolite allopregnanolone is a highly potent endogenous positive modulator of the GABA(A) receptor. Therefore, it is easy to envisage that allopregnanolone would have a hyperphagic effect, but earlier reports in rat have given ambiguous results. However, a contributing factor for the discrepancy may be the time point of the diurnal cycle in which the experiments were performed. The aim of this study was to investigate the effect of allopregnanolone on intake of standard chow in male Wistar rats at different time points of the day.

    Methods: Chow intake was measured after acute administration of allopregnanolone, and feeding behaviour was analysed to detect meal patterns.

    Results: We found that allopregnanolone increased chow intake by up to four times in the dark part of the 24-h cycle. The rats ate significantly more, and the effect of allopregnanolone was more prominent in the active (dark) compared with the inactive (light) period. Allopregnanolone also reduced feeding latency and prolonged the meal duration compared with vehicle.

    Conclusion: Allopregnanolone seems to act at several levels of feeding regulation, that is, to initiate feeding and to prolong the duration of a meal, thereby increasing the meal size, especially in the dark period of the 24-h cycle.

  • 5. Holtermann, A.
    et al.
    Grönlund, Christer
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Karlsson, J. Stefan
    Umeå University, Faculty of Science and Technology, Centre for Biomedical Engineering and Physics (CMTF).
    Roeleveld, Karin
    Differential activation of regions within the biceps brachii muscle during fatigue2008In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 192, no 4, p. 559-567Article in journal (Refereed)
    Abstract [en]

    Aim: To examine the occurrence of repeated differential activation between the heads of the biceps brachii muscle and its relation to fatigue prevention during a submaximal contraction.

    Methods: Thirty‐nine subjects carried out an isometric contraction of elbow flexion at 25% of maximal voluntary contraction (MVC) until exhaustion. A grid of 13 by 10 electrodes was used to record surface electromyographic signals from both heads of the biceps brachii. The root‐mean‐square of signals recorded from electrodes located medially and laterally was used to analyse activation differences. Differential activation was defined as periods of 33% different activation level between the two heads of the biceps brachii muscle.

    Results: Differential muscle activation was demonstrated in 30 of 33 subjects with appropriate data quality. The frequency of differential activation increased from 4.9 to 6.6 min−1 at the end of the contractions with no change in duration of the differential activations (about 1.4 s). Moreover, the frequency of differential activation was, in general, negatively correlated with time to exhaustion.

    Conclusion: The observed differential activation between the heads of the biceps brachii can be explained by an uneven distribution of synaptic input to the motor neurone pool. The findings of this study indicate that differential activation of regions within a muscle does not prevent fatigue at a contraction level of 25% of MVC.

  • 6.
    Jiang, Juan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Alstermark, Bror
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Dysfunctional cortico-reticulospinal and propriospinal systems may lead to impaired skilled forelimb reaching in EphA4-knockout mice2017In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 219, p. 34-35Article in journal (Refereed)
  • 7. Lebedeva, Albina
    et al.
    Zhuravleva, Zoya
    Denisov, Pavel
    Urazov, Mark
    Tovpuga, Vitaly
    Volnova, Anna
    Mironov, Andrey
    Mukhina, Irina
    Semyanov, Alexey
    Druzin, Michael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Mechanism of hypothalamus glycine receptor involvement in regulation of sexual behavior2016In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 217, p. 95-95Article in journal (Other academic)
  • 8. Meehan, CF
    et al.
    Moldovan, M
    Marklund, Stefan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Graffmo, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nielsen, JB
    Hultborn, H
    Intrinsic properties of lumbar motor neurones in the adult G127insTGGG superoxide dismutase-1 mutant mouse in vivo: evidence for increased persistent inward currents2010In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 200, no 4, p. 361-376Article in journal (Refereed)
    Abstract [en]

    We demonstrated that, in vivo, at resting membrane potential, spinal motor neurones of the adult G127X mice do not show an increased excitability. However, when depolarized they show evidence of an increased PIC and less SFA which may contribute to excitotoxicity of these neurones as the disease progresses.

  • 9.
    Mozibur, Rahman
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Zhu, Di
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Lindblad, Charlotte
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Johansson, Inga-Maj
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Holmberg, Elinor
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Isaksson, Monica
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Bäckström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Wang, Ming-De
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    GABA-site antagonism and pentobarbital actions do not depend on the α-subunit type in the recombinant rat GABA-A receptor2006In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 187, no 4, p. 479-488Article in journal (Refereed)
  • 10.
    Schrottmaier, Waltraud C.
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Institute for Vascular Biology and Thrombosis Research, Medical University of Vienna, Austria.
    Salzmann, M.
    Badrnya, S.
    Morava, S.
    Luik, A-L
    Kral-Pointner, J. B.
    Mussbacher, M.
    Karlsson, M.
    Forsell, Mattias
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Assinger, A.
    Platelet-stored antibodies potently diminish viral infection in vitro and in vivo2019In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 227, no S718, p. 187-187Article in journal (Other academic)
    Abstract [en]

    Besides their primary role in haemostasis, platelets are actively involved in immune responses as they respond to various inflammatory stimuli, including microbial infection. Further, platelets contain intracellular IgG, but their physiologic function remains unknown. Thus, we aimed to elucidate the function of platelet-derived IgGs and their effect on viral infections. Human and murine platelets contained IgG which were released upon shear stress. However, IgG loss did not correlate with P-Selectin exposure or CXCL4 release and α-granule deficient (Nbeal2-/-) platelets failed to show reduced IgG content and release, indicating an extragranular IgG storage site within platelets. While platelet IgG could derive from megakaryocytes that have taken up IgG from the bone marrow microenvironment, naïve platelets also took up IgG directly from plasma in vitro and in vivo. Murine platelets from anti-IAV IgG seropositive mice reduced IAV infection in vitro and in vivo more efficiently than plasma containing comparable IgG levels. Further, human platelets from anti-CMV IgG seropositive but not seronegative donors also potently neutralized in vitro CMV-infection of HUVEC under microvascular shear stress. Our data indicate that IgG storage in platelets may not be restricted to α-granules. Further, our results show that platelets have the potential to mediate potent IgG-mediated antiviral effects both in vitro and in vivo directly at foci of infection. This indicates that platelet-derived IgG may represent a yet unexplored mechanism for focused serological immunity.

  • 11.
    Stegmayr, Bernd G
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    New insight in impaired binding capacity for albumin in uraemic patients2015In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 215, no 1, p. 5-8Article in journal (Refereed)
  • 12.
    Waldenström, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Haney, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Biber, Björn
    Kavianipour, Mohammad
    Moritz, Thomas
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Strandén, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
    Wikström, Gerhard
    Ronquist, Gunnar
    Ischaemic preconditioning is related to decreasing levels of extracellular adenosine that may be metabolically useful in the at-risk myocardium: an experimental study in the pig2010In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 199, no 1, p. 1-9Article in journal (Refereed)
    Abstract [en]

    Aim: 'Pre-treatment' with short repetitive periods of ischaemia (ischaemic preconditioning) has proved to be a powerful mechanism for modification of the extent of myocardial damage following acute coronary artery occlusion. The exact mechanism of protection induced by ischaemic preconditioning is not known. We herewith put forward a contributing component for protection with preconditioning involving a shift in the adenylate kinase (AK) equilibrium reaction in favour of adenosine triphosphate (ATP) formation. Methods: A coronary artery was occluded in anaesthetized thoracotomized pigs to induce ischaemic preconditioning as well as a longer period of ischaemia. Microdialysis probes were inserted in ischaemic and control myocardium and were infused with (14)C- adenosine with two different specific activities. (14)C-lactate was identified and measured in the effluent. Results: (14)C-adenosine was taken up by non-preconditioned and preconditioned myocardium during ischaemia. Significantly increased levels of (14)C-lactate were recovered in preconditioned myocardium. (14)C-adenosine with high specific activity resulted in a specific activity of lactate that was 2.7 times higher than that of lactate after administration of (14)C-adenosine with low specific activity. Mass spectrography verified the identity of (14)C-lactate. Conclusions: Preconditioning up-regulates a new metabolic pathway (starting with 5'-nucleotidase and ending up with lactate) resulting in ATP formation in the micromolar range on top of another effect terminating in a useful shift in the AK equilibrium reaction in favour of ATP generation in the millimolar range. Although the up-regulation of the purine nucleoside phosphorylase pathway is clearly demonstrated, its biological relevance remains to be proved.

  • 13.
    Wang, Ming-De
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Rahman, Mozibur
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Zhu, Di
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Backström, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynaecology.
    Pregnenolone sulfate and zinc inhibit recombinant rat GABAA receptor through different channel property2006In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 188, no 3/4, p. 153-163Article in journal (Refereed)
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