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  • 101. Holtermann, Andreas
    et al.
    Roeleveld, Karin
    Karlsson, J Stefan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Inhomogeneities in muscle activation reveal motor unit recruitment2005In: J Electromyogr Kinesiol, ISSN 1050-6411, Vol. 15, no 2, p. 131-137Article in journal (Refereed)
  • 102. Hugoson-Seligsohn, E E
    et al.
    Koskinen, L O
    TRH-induced blood flow and mean arterial pressure changes in the rabbit are not dependent on the anaesthetic used.1989In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 97, no 1, p. 190-6Article in journal (Refereed)
    Abstract [en]

    1. The effects of thyrotropin releasing hormone (TRH) on regional cerebral blood flow were studied in rabbits anaesthetized with pentobarbitone or ketamine. The blood flow was determined with the labelled microsphere method before and after the i.v. administration of either 50 micrograms kg-1 or 2 mg kg-1 TRH. 2. In order to measure the cerebral O2 consumption the arteriovenous difference in oxygen saturation in the brain (CAVOD) was measured before and after the administration of 2 mg kg-1 TRH. 3. In animals under pentobarbitone anaesthesia 50 micrograms kg-1 TRH elicited an increase in mean arterial blood pressure (MAP) of about 1 kPa and 2 mg kg-1 TRH elevated the MAP by about 2 kPa. With ketamine as the anaesthetic the corresponding values were 0.5 kPa and 7 kPa, respectively. TRH induced significant vasoconstriction in several peripheral tissues. 4. The total cerebral blood flow (CBFtot) increased from 54 +/- 4 to 78 +/- 5 g min-1 100 g-1 after the administration of 50 micrograms kg-1 TRH in pentobarbitone-anaesthetized animals. An even greater effect was elicited by 2 mg kg-1 TRH, from 48 +/- 6 to 113 +/- 19 g min-1 100 g-1. In ketamine-anaesthetized rabbits, 50 micrograms kg-1 TRH tended to enhance the CBFtot and 2 mg kg-1 increased it from 71 +/- 6 to 141 +/- 19 g min-1 100 g-1. 5. In animals anaesthetized with pentobarbitone, the CAVOD decreased from 47.3 +/- 1.7% to 35.1 +/- 2.2% at 3 min after TRH delivery, and then gradually increased to the control level. In animals under ketamine anaesthesia the CAVOD decreased from 63.3 + 2.0% to 45.2 + 7.4% after the administration of 2 mg kg'- TRH. 6. It is concluded that TRH elicits cerebral vasodilatation in excess of that required by the change in cerebral metabolism which may have taken place. The pattern of responses was similar to that produced in rabbits under urethane anaesthesia.

  • 103.
    Huttu, Mari
    et al.
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Turunen, Siru
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Sokolinski, Viktoria
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Tiitu, Virpi
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; SIB-Labs, University of Eastern Finland, Kuopio, Finland.
    Lammi, Mikko
    Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland.
    Korhonen, Rami K
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Effects of medium and temperature on cellular responses in the superficial zone of hypo-osmotically challenged articular cartilage.2012In: Journal of Functional Biomaterials, ISSN 2079-4983, Vol. 3, no 3, p. 544-555, article id 23807905Article in journal (Refereed)
    Abstract [en]

    Osmotic loading of articular cartilage has been used to study cell-tissue interactions and mechanisms in chondrocyte volume regulation in situ. Since cell volume changes are likely to affect cell's mechanotransduction, it is important to understand how environmental factors, such as composition of the immersion medium and temperature affect cell volume changes in situ in osmotically challenged articular cartilage. In this study, chondrocytes were imaged in situ with a confocal laser scanning microscope (CLSM) through cartilage surface before and 3 min and 120 min after a hypo-osmotic challenge. Samples were measured either in phosphate buffered saline (PBS, without glucose and Ca(2+)) or in Dulbecco's modified Eagle's medium (DMEM, with glucose and Ca(2+)), and at 21 °C or at 37 °C. In all groups, cell volumes increased shortly after the hypotonic challenge and then recovered back to the original volumes. At both observation time points, cell volume changes as a result of the osmotic challenge were similar in PBS and DMEM in both temperatures. Our results indicate that the initial chondrocyte swelling and volume recovery as a result of the hypo-osmotic challenge of cartilage are not dependent on commonly used immersion media or temperature.

  • 104.
    Häger Ross, Charlotte
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    To grip and not to slip: sensorimotor mechanisms in reactive control of grasp stability1995Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The reactive control of fingertip forces maintaining grasp stability was examined in man during a prehensile task. Blindfolded subjects used the precision grip between the tips of index finger and thumb to restrain an object that was subjected to unpredictable load forces. These were delivered tangential to the parallel grip surfaces of the object. Load forces, grip forces (perpendicular to the grip surfaces) and position of the object were recorded.Subjects automatically adjusted the grip forces to loads of various amplitudes and rates. Thereby they maintained a reliable safety margin against frictional slips without using excessive grip forces. A rapid rise in grip force lasting about 0.2 s was triggered after a short delay following the onset of a sustained ramp load increase. This 'catch-up' response caused a quick restoration of an adequate grip:load force ratio that prevented frictional slips. If the ramp load continued to increase after the catchup response, the grip force also increased in parallel with the load change in a 'tracking' manner. Consequently, during the hold phases of 'ramp-and-hold' loads, the employed grip forces were approximately proportional to the load amplitude. Sensory information about the rate of change of the load force parametrically scaled the 'catchup' and 'tracking' responses.Following anesthetic block of sensory input from the digits, the grip responses were both delayed and attenuated or even abolished. To compensate for these impairments, subjects had to voluntarily maintain exceedingly high grip forces to prevent the object from slipping. The grip control improved slightly during hand and forearm support conditions that allowed marked wrist movements to occur in response to the loading. This indicates that signals from receptors in muscles, joints or skin areas proximal to the digits can to some extent be used to adjust grip forces during impaired digital sensibility. In contrast, these signals had only minor influence on the control during normal digital sensibility.Grip responses to loads delivered in various directions revealed that the load direction, in relation to gravity and to the hand's geometry, represents intrinsic task variables in the automatic processes that maintain a stable grasp. The load direction influenced both the response latencies and the magnitudes of the grip responses. The response latencies were shortest for loads in directions that were the most critical with regard to the consequences of frictional slippage, i.e., loads directed away from the palm or in the direction of gravity. Recordings of signals in cutaneous afferents innervating the finger tips demonstrated that these effects on the response latencies depended on differences in the time needed by the central nervous system to implement the motor responses. The short latencies in the most ‘criticar load directions may reflect the preparation of a default response, while additional central processing would be needed to execute the response to loads in other directions. Adjustments to local frictional anisotropies at the digit-object interface largely explained the magnitude effects.In conclusion, grip responses are automatically adjusted to the current loading condition during unpredictable loading of a hand held object. Subjects call up a previously acquired sensorimotor transform that supports grasp stability by preventing both object slippage and excessive grip forces. Cutaneous sensory information about tangential forces and frictional conditions at the digit-object interface is used to initiate and scale the grip responses to the current loading conditions, largely in a predictive manner.

  • 105.
    Hörnsten, Rolf
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences.
    Cardiac arrhythmias and heart rate variability in familial amyloidotic polyneuropathy: A clinical study before and after liver transplantation2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Familial amyloidotic polyneuropathy (FAP), found in the northernmost counties in Sweden, is a rare, lethal and inherited amyloidosis. The disease is caused by mutated transthyretin (TTR). The mutation is characterized by an exchange of valine for methionine at position 30 (ATTRVal30Met). FAP is characterised by progressive polyneuropathy affecting both the peripheral and autonomic nervous system (ANS). Cardiac arrhythmia and autonomic disturbances are common as well as gastrointestinal symptoms: such as constipation and diarrhoea.

    Today, orthotopic liver transplantation (LTx) is the only treatment to stop the progression of FAP. The rationale for this is because 95% of TTR is synthesized by the liver, a liver transplantation should abolish the production of new mutated amyloidogenic TTR. The first liver transplantation for FAP was performed in Sweden 1990.

    Heart complications and autonomic disturbances are common in FAP patients both before and after liver transplantation. The aim of the present study was three-fold: to determine whether liver transplantation affects the natural course of cardiac arrhythmias and cardiac autonomic function; to predict the risk of ventricular arrhythmias; and to elucidate heart rate variability (HRV) patterns by power spectrum analysis and Poincaré plots.

    In total, ninety-seven Swedish FAP patients were included in the studies. The patients underwent 24-hours electrocardiography (Holter) recordings, and/or signal averaged electrocardiography (SAECG) and heart rate variability.

    The study showed that many patients developed cardiac arrhythmias and conduction disturbances after LTx. Approximately 25 percent of patients were pacemaker treated after LTx. The SAECG recordings disclosed that many FAP patients had ventricular late potentials (LP) compared with healthy subjects, and that LP were associated with nonsustained ventricular arrhythmia. Analyses of heart rate variability (HRV) showed reduced autonomic function in the majority of patients. Some patients had high HRV with broadband power spectra and Poincaré graphs with a fan or complex pattern. These novel findings could be an indicator of ECG abnormalities (subtle atrial arrhythmia) in FAP patients instead of reflecting normal cardiac autonomic modulation. The HRV studies also showed that LTx preserves cardiac autonomic function in FAP.

    In conclusion, cardiac arrhythmias, late potentials and reduced heart rate variability were common in Swedish patients with FAP, whether they underwent liver transplantation or not. The absence of LP may indicate a low risk for ventricular tachycardia in FAP patients.

  • 106. Idborg, Helena
    et al.
    Oliynyk, Ganna
    Rännar, Stefan
    AcureOmics AB.
    Forshed, Jenny
    Branca, Rui Mamede
    Donten, Magdalena
    Gustafsson, Johanna
    Vikerfors, Anna
    Gunnarsson, Iva
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lehtiö, Janne
    Lundstedt, Torbjörn
    Svenungsson, Elisabet
    Jakobsson, Per-Johan
    Systems biology of SLE: biochemical characterisation of subgroups within SLE for improved diagnosis and treatment2012In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 71, p. A12-Article in journal (Other academic)
  • 107.
    Jeneskog, Torgny
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    A descending pathway to dynamic fusimotor neurones and its possible relation to a climbing fibre system1974Doctoral thesis, comprehensive summary (Other academic)
  • 108.
    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)
  • 109.
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Context dependent adaptation of biting behavior in human2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The focus of this thesis was to study an action that humans perform regularly, namely, to hold a morsel between the teeth and split it into smaller pieces. Three different issues related to this biting behavior were addressed:  (1) the effect of redu­c­ed perio­dontal tissues on food holding and splitting behavior; (2) the behavioral conse­quences of performing different bite tasks with different functional requirements, i.e., to split a peanut half resting on a piece of chocolate or to split both the peanut and the chocolate; and (3) the reflex modulations resul­ting from such a change in the intended bite action. The main conclusions from the experi­mental studies were the following:

    First, perio­dontitis, an inflam­matory disease that destroys the peri­o­dontal ligaments and the embedded perio­dontal mechanoreceptors, causes significant impairments in the masticatory abili­ty: the manipulative bite forces when holding a morsel are elevated compared to a matched control population and the bite force development prior to food split is altered. These changes are likely due to a combination of reduced sensory informa­tion from the damaged ligaments and to changes in the bite stra­tegy secon­d­ary to the unstable oral situation.

    Second, people exploit the anatomy of jaw-closing muscles to regulate the amount of bite force that dissipates following a sudden unloading of the jaw. Such control is necessary because without mechanisms that quickly halt jaw-closing movements after sudden unloading, the impact forces when the teeth collide could otherwise damage both the teeth and related soft tissues. Splitting a piece of chocolate, for instance, regularly requires >100N of bite force and the jaws collide within 5 ms of a split. On the other hand, when biting through heterogeneous food, the bite force needs to be kept high until the whole morsel is split. The required regulation is achieved by differen­tial­ly engaging parts of the masseter muscles along the anteroposterior axis of the jaw to exploit differences between muscle portions in their bite force generating capa­ci­ty and muscle shortening velocity.

    Finally, the reflex evoked by suddenly unloading the jaw—apparent only after the initial bite force dissipation—is modulated according to the bite intention. That is, when the intention is to bite through food items with multiple layers, the reflex response in the jaw opening muscles following a split is small, thus minimizing the bite force reduction. In contrast, when the intention is to rapidly decrease the bite force once a split has occurred, the reflex response is high. This pattern of reflex modulation is functionally beneficial when biting through heterogeneous food in a smooth manner.

    The presented studies show the significance of integrating cogni­tive, physiological and anatomical aspects when attempting to understand human masticatory control.

  • 110.
    Johansson, Anders Sixten
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Pruszynski, J Andrew
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Edin, Benoni Benjamin
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Westberg, Karl-Gunnar
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Biting intentions modulate digastric reflex responses to sudden unloading of the jaw2014In: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 112, no 5, p. 1067-1073Article in journal (Refereed)
    Abstract [en]

    Reflex responses in jaw opening muscles can be evoked when a brittle object cracks between the teeth and suddenly unloads the jaw. We hypothesized that this reflex response is flexible and, as such, is modulated according to the instructed goal of biting through an object. Study participants performed two different biting tasks when holding a peanut-half stacked on a chocolate piece between their incisors. In one task, they were asked to split the peanut-half only (single-split task) and, in the other task, they were asked to split both the peanut and the chocolate in one action (double-split task). In both tasks, the peanut split evoked a jaw opening muscle response, quantified from EMG recordings of the digastric muscle in a window 20-60 ms following peanut split. Consistent with our hypothesis, we found that the jaw opening muscle response in the single-split trials was about twice the size of the jaw opening muscle response in the double-split trials. A linear model that predicted the jaw opening muscle response on a single trial basis indicated that task settings played a significant role in this modulation but also that the pre-split digastric muscle activity contributed to the modulation. These findings demonstrate that, like reflex responses to mechanical perturbations in limb muscles, reflex responses in jaw muscles not only show gain-scaling but also are modulated by subject intent.

  • 111.
    Johansson, Anders
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Westberg, Karl-Gunnar
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Edin, Benoni B.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Task-dependent control of the jaw during food splitting in humans2014In: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 111, p. 2614-2623Article in journal (Refereed)
    Abstract [en]

    Although splitting of food items between the incisors often requires high bite forces, rarely do the teeth harmfully collide when the jaw quickly closes after split. Previous studies indicate that the force-velocity relationship of the jaw closing muscles principally explains the prompt dissipation of jaw closing force. Here, we asked whether people could regulate the dissipation of jaw closing force during food splitting. We hypothesized that such regulation might be implemented via differential recruitment of masseter muscle portions situated along the anteroposterior axis because these portions will experience a different shortening velocity during jaw closure. Study participants performed two different tasks when holding a peanut-half stacked on a chocolate piece between their incisors. In one task, they were asked to split the peanut-half only (single-split trials) and, in the other, to split both the peanut and the chocolate in one action (double-split trials). In double-split trials following the peanut split, the intensity of the tooth impact on the chocolate piece was on average 2.5 times greater than in single-split trials, indicating a substantially greater loss of jaw closing force in the single-split trials. We conclude that control of jaw closing force dissipation following food splitting depends on task demands. Consistent with our hypothesis, converging neurophysiological and morphometric data indicated that this control involved a differential activation of the jaw closing masseter muscle along the anteroposterior axis. These latter findings suggest that the regulation of jaw closing force after sudden unloading of the jaw exploits masseter muscle compartmentalization.

  • 112.
    Johansson, Marie-Louise
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Berthilsson, Matilda
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Samband mellan psykologiska och fysiska faktorer hos patienter med utmattningssyndrom2012Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Introduktion: Långvarig stressbelastning utan möjlighet till adekvat återhämtning kanleda till ett antal sjukdomar som exempelvis utmattningssyndrom (UMS). Goda kunskaper finns idag om patienter med utmattningssyndrom och deras mentala hälsa, men fortfarande saknas kunskap om sambandet med deras fysiska status.Syfte: Syftet med denna studie var att studera samband mellan psykologiska och fysiska variabler hos patienter med utmattningssyndrom.Metod: Utgångsvärden samlades in från en randomiserad kontrollerad studie (ForRest). Studiepopulationen bestod av 99 patienter (85 kvinnor och 14 män) med en medelålder på 44,6 ± 8,6 år, samtliga med diagnosen utmattningssyndrom.Resultat: Signifikant samband påvisades mellan trötthet och konditionsvärde, VO2max, samt dynamisk balans. De patienter som skattade en högre grad av trötthet hade ett lägre VO2-max, ett lägre konditionsvärde samt lägre dynamisk balans.Konklusion: Patienter med UMS har olika utgångslägen vad gäller mental och fysisktstatus och det gäller att möta dessa varierade behov för att hitta en balans mellan vila och regelbunden motion. Därmed kan sjukgymnasten vara en viktig yrkesgrupp i både prevention samt rehabilitering av patienter med utmattningssyndrom.

  • 113.
    Johansson, Mikael
    et al.
    Departments of Oncology, University Hospital, Umeå, Sweden.
    Bergenheim, A. Tommy
    Departments of Oncology, University Hospital, Umea, Sweden. Neurosurgery, University Hospital, Umeå, Sweden.
    Henriksson, Roger
    Departments of Oncology, University Hospital, Umea, Sweden.
    Koskinen, Lars-Owe D.
    Neurosurgery, University Hospital, Umeå, Sweden.
    Vallbo, Christina
    Departments of Oncology, University Hospital, Umea, Sweden.
    Widmark, Anders
    Departments of Oncology, University Hospital, Umea, Sweden.
    Tumor blood flow and the cytotoxic effects of estramustine and its constituents in a rat glioma model.1997In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 41, no 1, p. 237-244Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Estramustine (EaM) is a conjugate of nor-nitrogen mustard (NNM) and 17 beta-estradiol (E2) that has cytotoxic and radiosensitizing effects on experimental malignant glioma. Its mechanism of action is only partly understood. To further investigate the mechanism in vivo, the effects on tumor blood flow (TBF) and tumor growth were analyzed.

    METHODS: TBF was measured by radioactive microspheres, and tumor growth was measured by weight. Apoptosis was evaluated by in situ end labeling and gel electrophoresis. The effects of the constituents NNM and E2 were also evaluated.

    RESULTS: EaM increased TBF to 153.8 ml/100 g/min after 3 days and to 153.9 ml/100 g/min after 10 days of treatment, compared with 94.0 ml/100 g/min in untreated controls. Cerebral blood flow did not change after EaM treatment. NNM increased TBF but also showed a tendency to increase cerebral blood flow. E2 increased TBF, whereas cerebral blood flow was unchanged. EaM resulted in a rapid reduction in tumor weight from 230 mg in untreated animals to 146 mg after 3 days of treatment. EaM induced an early transient fragmentation of deoxyribonucleic acid in glioma but not in the normal brain. Neither NNM nor E2 affected tumor weight.

    CONCLUSION: EaM increases TBF in the BT4C rat glioma model with a concomitant rapid antitumoral effect. The increase in TBF could partially be induced by an estrogen-like action of EaM, but the rapid cytotoxic effect of the drug is obviously attributed to the intact EaM compound. This cytotoxic effect might be attributable to the induction of programmed cell death.

  • 114.
    Johansson, R S
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Westling, G
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Bäckström, A
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Flanagan, J R
    Queen's University, Kingston, Canada.
    Eye-hand coordination in object manipulation.2001In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 21, no 17, p. 6917-32Article in journal (Refereed)
    Abstract [en]

    We analyzed the coordination between gaze behavior, fingertip movements, and movements of the manipulated object when subjects reached for and grasped a bar and moved it to press a target-switch. Subjects almost exclusively fixated certain landmarks critical for the control of the task. Landmarks at which contact events took place were obligatory gaze targets. These included the grasp site on the bar, the target, and the support surface where the bar was returned after target contact. Any obstacle in the direct movement path and the tip of the bar were optional landmarks. Subjects never fixated the hand or the moving bar. Gaze and hand/bar movements were linked concerning landmarks, with gaze leading. The instant that gaze exited a given landmark coincided with a kinematic event at that landmark in a manner suggesting that subjects monitored critical kinematic events for phasic verification of task progress and subgoal completion. For both the obstacle and target, subjects directed saccades and fixations to sites that were offset from the physical extension of the objects. Fixations related to an obstacle appeared to specify a location around which the extending tip of the bar should travel. We conclude that gaze supports hand movement planning by marking key positions to which the fingertips or grasped object are subsequently directed. The salience of gaze targets arises from the functional sensorimotor requirements of the task. We further suggest that gaze control contributes to the development and maintenance of sensorimotor correlation matrices that support predictive motor control in manipulation.

  • 115.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Dynamic use of tactile afferent signals in control of dexterous manipulation.2002In: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 508, p. 397-410Article in journal (Refereed)
    Abstract [en]

    During object manipulation, humans select and activate neural action programs acquired during ontogenetic development. A basic issue in understanding the control of dexterous manipulation is to learn how people use sensory information to adapt the output of these neural programs such that the fingertip actions matches the requirements imposed by the physical properties of the manipulated object, e.g., weight (mass), slipperiness, shape, and mass distribution. Although visually based identification processes contribute to predictions of required fingertip actions, the digital tactile sensors provide critical information for the control of fingertip forces. The present account deals with the tactile afferent signals from the digits during manipulation and focuses on some specific issues that the neural controller has to deal with to make use of tactile information.

  • 116.
    Johansson, Roland S
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Flanagan, J Randall
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Coding and use of tactile signals from the fingertips in object manipulation tasks2009In: Nature Reviews Neuroscience, ISSN 1471-003X, E-ISSN 1471-0048, Vol. 10, no 5, p. 345-359Article in journal (Refereed)
    Abstract [en]

    During object manipulation tasks, the brain selects and implements action-phase controllers that use sensory predictions and afferent signals to tailor motor output to the physical properties of the objects involved. Analysis of signals in tactile afferent neurons and central processes in humans reveals how contact events are encoded and used to monitor and update task performance.

  • 117.
    Johansson, Roland S
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Flanagan, JR
    Sensory control of object manipulation2009In: Sensorimotor control of grasping: Physiology and pathophysiology / [ed] Dennis A. Nowak, Joachim Hermsdörfer., Cambridge: Cambridge books , 2009, p. 141-160Chapter in book (Other (popular science, discussion, etc.))
    Abstract [en]

    Series of action phases characterize natural object manipulation tasks where each phase is responsible for satisfying a task subgoal. Subgoal attainment typically corresponds to distinct mechanical contact events, either involving the making or breaking of contact between the digits and an object or between a held object and another object. Subgoals are realized by the brain selecting and sequentially implementing suitable action-phase controllers that use sensory predictions and afferents signals in specific ways to tailor the motor output in anticipation of requirements imposed by objects' physical properties. This chapter discusses the use of tactile and visual sensory information in this context. It highlights the importance of sensory predictions, especially related to the discrete and distinct sensory events associated with contact events linked to subgoal completion, and considers how sensory signals influence and interact with such predictions in the control of manipulation tasks.

  • 118.
    Johansson, Staffan
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Yelhekar, Tushar D.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Druzin, Michael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Commentary: Chloride Regulation: a Dynamic Equilibrium Crucial for Synaptic Inhibition2016In: Frontiers in Cellular Neuroscience, ISSN 1662-5102, E-ISSN 1662-5102, Vol. 10, article id 182Article in journal (Refereed)
  • 119.
    Jönsson, Axel
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Thudén, Rebecca
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Genomförbarheten av mentorledd träning av äldre på ett svenskt seniorboende2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Bakgrund: Trots att Sveriges befolkning ökar i medellivslängd finns det få fungerande preventiva insatser som, ur ett samhällsekonomiskt perspektiv, har huvudfokus på att effektivisera träningen för äldre. Preventiva insatser med målet att öka äldres muskelstyrka och på så sätt minska den degenerativa processen används i dagsläget i för liten utsträckning. Därför blir behovet av anpassade fysioterapeutiska insatser större då andelen äldre väntas öka.

    Syfte: Undersöka genomförbarheten av tio veckors mentorledd träning i ett seniorboende för 55+ år.

    Metod: En genomförbarhetsstudie med kvantitativ och kvalitativ karaktär. Trettiotvå personer rekryterades och delades in i fyra träningsgrupper. Fyra personer värvades som mentorer till var sin träningsgrupp som tränade tre gånger i veckan under tio veckor. Testning av timed up and go (TUG), chairstand 30 sekunder och sex minuters gångtest genomfördes före och efter träningsperioden, samt fokusgruppintervjuer som hölls mot slutet av interventionen. Cirkelträningsprogrammet bestod av åtta övningar som inkluderade stora delar av kroppen. Övningarna utfördes i bestämd ordningsföljd med inledningsvis 3x30 sekunders arbete per station och 15 sekunders vila mellan varje set. Upplägget innefattade styrkeövningar som på olika sätt medförde balans- och konditionsträning.

    Resultat: Interventionen hade en närvaro på 83%, med tre avhopp. Samtliga tester visade på signifikanta förbättringar (p <0,001). I fokusgruppintervjuerna framkom det att deltagarna upplevde fysiska samt psykiska förbättringar som förbättrad balans och ökat välmående. Dessutom gav gruppträningen samhörighet bland deltagarna.

    Slutsats: Resultaten utifrån fysiska tester och fokusgruppintervjuer tyder på goda förutsättningar för genomförbarheten av mentorledd träning för äldre samt möjlighet till fortsatt användning som preventiv metod.

  • 120. Jönsson, Sofia
    et al.
    Becirovic-Agic, Mediha
    Isackson, Henrik
    Tveitarås, Maria K.
    Skogstrand, Trude
    Narfström, Fredrik
    Karlsen, Tine, V
    Lidén, Åsa
    Leh, Sabine
    Ericsson, Madelene
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Nilsson, Stefan K.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Reed, Rolf K.
    Hultström, Michael
    Angiotensin II and salt-induced decompensation in Balb/CJ mice is aggravated by fluid retention related to low oxidative stress2019In: American Journal of Physiology - Renal Physiology, ISSN 1931-857X, E-ISSN 1522-1466, Vol. 316, no 5, p. F914-F933Article in journal (Refereed)
    Abstract [en]

    Balb/CJ mice are more sensitive to treatment with angiotensin II (ANG II) and high-salt diet compared with C57BL/6J mice. Together with higher mortality, they develop edema, signs of heart failure, and acute kidney injury. The aim of the present study was to identify differences in renal gene regulation that may affect kidney function and fluid balance, which could contribute to decompensation in Balb/CJ mice after ANG II + salt treatment. Male Balb/CJ and C57BL/6J mice were divided into the following five different treatment groups: control, ANG II, salt, ANG II + salt. and ANG II + salt + N-acetylcysteine. Gene expression microarrays were used to explore differential gene expression after treatment and between the strains. Published data from the Mouse Genome Database were used to identify the associated genomic differences. The glomerular filtration rate (GFR) was measured using inulin clearance, and fluid balance was measured using metabolic cages. Gene ontology enrichment analysis of gene expression microarrays identified glutathione transferase (antioxidant system) as highly enriched among differentially expressed genes. Balb/CJ mice had similar GFR compared with C57BL/6J mice but excreted less Na+ and water, although net fluid and electrolyte balance did not differ, suggesting that Balb/CJ mice may be inherently more prone to decompensation. Interestingly, C57BL/6J mice had higher urinary oxidative stress despite their relative protection from decompensation. In addition, treatment with the antioxidant N-acetylcysteine decreased oxidative stress in C57BL/6J mice, reduced urine excretion, and increased mortality. Balb/CJ mice are more sensitive than C57BL/6J to ANG II + salt, in part mediated by lower oxidative stress, which favors fluid and Na+ retention.

  • 121.
    Kantola, Leila
    et al.
    Umeå University, Faculty of Arts, Department of language studies.
    Piccolino, Marco
    Wade, Nicholas J.
    The action of light on the retina: Translation and commentary of Holmgren (1866)2019In: Journal of the History of the Neurosciences, ISSN 0964-704X, E-ISSN 1744-5213, Vol. 28, no 4, p. 399-415Article in journal (Refereed)
    Abstract [en]

    In 1866, Holmgren published an account of the physiological action of light on the retina. The article is taken as the origin of research on the electroretinogram, although the term was not introduced until much later. We present a translation of the article into English and provide a commentary on its reception and significance.

  • 122.
    Karlsson, Britt M.
    et al.
    Defence Research Establishment, Division of NBC Defence, 5‐907 82 Umeå, Sweden.
    Waara, Lena M.
    Defence Research Establishment, Division of NBC Defence, 5‐907 82 Umeå, Sweden.
    Fredriksson, Sten-Åke
    Koskinen, Lars-Owe D.
    Department of Neurosurgery, University Hospital of Umeå, S‐901 85 Umeå, Sweden.
    The effect of the calcium antagonist nimodipine on the detoxification of soman in anaesthetized rabbits.1997In: Journal of Pharmacy and Pharmacology (JPP), ISSN 0022-3573, E-ISSN 2042-7158, Vol. 49, no 3, p. 296-300Article in journal (Refereed)
    Abstract [en]

    The effect of nimodipine, a vasoactive calcium antagonist, on the disappearance of soman from blood was studied in anaesthetized rabbits intoxicated with soman (10.8 micrograms kg-1 i.v.). Blood samples from the left heart ventricle and femoral artery were used to investigate soman detoxification. The concentrations of the soman isomers C+P- and C-P- in blood samples were determined by gas chromatography coupled with high-resolution mass spectrometry. During the sampling, 15-300 s after soman injection, the soman concentration in control animals decreased from 50 to 0.029 ng mL-1; in animals pre-treated with nimodipine (10 mg kg-1) it decreased from 15 to 0.033 ng mL-1. In animals pre-treated with nimodipine the soman concentration was significantly reduced during the first minute of sampling. No differences were detected between soman concentrations in samples from the heart and femoral artery. Acetylcholinesterase inhibition was also used as an indicator of soman activity; there was no difference between the activity of this enzyme in different peripheral organs of control and nimodipine-treated animals. Nimodipine reduces the initial concentration of soman in the blood, which might be of significance in the treatment of soman intoxication.

  • 123.
    Karlsson, Linnea
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Wiklund-Hornqvist, Carola
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Jonsson, Bert
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Retrieval practice is characterized by reduced fronto-striatal activity2013In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 25, no Suppl., p. S82-S83Article in journal (Other academic)
  • 124.
    Karlsson, Sari
    et al.
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Karlsson, Per
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, Stockholm, Sweden.
    Fischer, Håkan
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Thilers, Petra
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    MacDonald, Stuart
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Brehmer, Yvonne
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Rieckmann, Anna
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Halldin, Christer
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, Stockholm, Sweden.
    Farde, Lars
    Department of Clinical Neuroscience, Psychiatry Section, Karolinska Hospital, Stockholm, Sweden.
    Bäckman, Lars
    Aging Research Center, Karolinska Institutet, Stockholm, Sweden.
    Modulation of striatal dopamine D1 binding by cognitive processing2009In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 48, no 2, p. 398-404Article in journal (Refereed)
    Abstract [en]

    There is strong evidence that dopamine (DA) is implicated in higher-order cognitive functioning, but it remains controversial whether D1 receptor binding can be modified by cognitive activity. We examined striatal D1 binding potential (BP) in 20 younger (22-30 years) and 20 older (65-75 years) persons who underwent two [(11)C] SCH 23390 PET measurements, one while resting and one while performing a cognitive task taxing inhibitory functioning. The younger persons showed significant task-related BP reductions in sensorimotor, limbic, and associative striatum during cognitive activity compared to rest. Older persons showed no reliable BP reductions in any striatal subregion. These findings demonstrate that D1 receptor binding can be modified by cognitive activity in younger persons, but also provide novel evidence for the notion that human aging is associated not only with lower DA receptor density but also with altered modifiability of the DA system.

  • 125.
    Karlsson, Urban
    Umeå University, Faculty of Medicine, Integrative Medical Biology.
    GABA-, glycine- and glutamate-induced currents in rat medial preoptic neurons: functional interactions and modulation by capsaicin2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The medial preoptic nucleus (MPN) of the hypothalamus plays a major role in many functions involved in maintaining bodily homeostasis, such as thermoregulation and osmoregulation, as well as in the control of complex behaviours, e.g. sexual behaviour. A fundamental basis for the control and execution of these functions is the synaptic communication between neurons of the MPN. However, the functional properties of the synapses involved are largely unknown. The present thesis is a study of ligand-gated ion channels involved in the pre- and post-synaptic aspects of neuronal communication in the MPN of rat. The aim was to clarify synaptic properties in the MPN, to identify the major channel types involved and to obtain a better understanding of their functional properties.

    By fast application of agonists to isolated neurons, it was first demonstrated that all neurons responded to glutamate with currents mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and a majority of neurons also with currents mediated by N-Methyl-D-aspartate (NMDA) receptors. All neurons also responded to γ-aminobutyric acid (GABA) and glycine with currents mediated by GABAA receptors and glycine receptors, respectively. These findings show that fast-acting excitatory and inhibitory amino-acid transmitters are most likely important for communication between hypothalamic neurons.

    Application of agonists to isolated neurons revealed cross-talk, detected as an apparent cross-desensitization, between the responses to GABA and those to glycine. Parallel analysis of current and conductance, using gramicidin-perforated patches to avoid perturbing intracellular chloride concentration, showed that the cross-talk was not dependent on a direct interaction between the receptors as previously suggested, but was a consequence of the change in the intracellular chloride concentration during receptor activation. Strengthened by a computer model, the analysis also showed that the current decay in the presence of GABA or glycine was mainly due to a change in the chloride driving force and that receptor desensitization played a minor role only.

    The role of thermo-sensitive transient receptor potential TRPV1 channels in the regulation of glutamate- and GABA-mediated transmission was studied in the slice preparation, where much of the synaptic connections between neurons are preserved. It was shown that application of the TRPV1 agonist capsaicin increased the frequency of excitatory AMPA receptor- mediated as well as inhibitory GABAA receptor-mediated postsynaptic currents. This effect was partly presynaptic and demonstrates that TRP channels play a role in regulating synaptic transmission in the MPN. The results imply that such mechanisms may possibly contribute to the thermoregulation by MPN neurons.

  • 126.
    Karlsson, Urban
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Druzin, Michael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Johansson, Staffan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Cl concentration changes and desensitization of GABAA and glycine receptors2011In: The Journal of General Physiology, ISSN 0022-1295, E-ISSN 1540-7748, Vol. 138, no 6, p. 609-626Article in journal (Refereed)
    Abstract [en]

    Desensitization of ligand-gated ion channels plays a critical role for the information transfer between neurons. The current view on γ-aminobutyric acid (GABA)A and glycine receptors includes significant rapid components of desensitization as well as cross-desensitization between the two receptor types. Here, we analyze the mechanism of apparent cross-desensitization between native GABAA and glycine receptors in rat central neurons and quantify to what extent the current decay in the presence of ligand is a result of desensitization versus changes in intracellular Cl concentration ([Cl]i). We show that apparent cross-desensitization of currents evoked by GABA and by glycine is caused by changes in [Cl]i. We also show that changes in [Cl]i are critical for the decay of current in the presence of either GABA or glycine, whereas changes in conductance often play a minor role only. Thus, the currents decayed significantly quicker than the conductances, which decayed with time constants of several seconds and in some cells did not decay below the value at peak current during 20-s agonist application. By taking the cytosolic volume into account and numerically computing the membrane currents and expected changes in [Cl]i, we provide a theoretical framework for the observed effects. Modeling diffusional exchange of Cl between cytosol and patch pipettes, we also show that considerable changes in [Cl]i may be expected and cause rapidly decaying current components in conventional whole cell or outside-out patch recordings. The findings imply that a reevaluation of the desensitization properties of GABAA and glycine receptors is needed.

  • 127.
    Karlsson Wirebring, Linnea
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Social Sciences, Department of Psychology.
    Wiklund-Hörnqvist, Carola
    Umeå University, Faculty of Social Sciences, Department of Psychology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Eriksson, Johan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Jonsson, Bert
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Lesser neural pattern similarity across repeated tests is associated with better long-term memory retention2015In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 35, no 26, p. 9595-9602Article in journal (Refereed)
    Abstract [en]

    Encoding and retrieval processes enhance long-term memory performance. The efficiency of encoding processes has recently been linked to representational consistency: the reactivation of a representation that gets more specific each time an item is further studied. Here we examined the complementary hypothesis of whether the efficiency of retrieval processes also is linked to representational consistency. Alternatively, recurrent retrieval might foster representational variability—the altering or adding of underlying memory representa- tions. Human participants studied 60 Swahili–Swedish word pairs before being scanned with fMRI the same day and 1 week later. On Day 1, participants were tested three times on each word pair, and on Day 7 each pair was tested once. A BOLD signal change in right superior parietal cortex was associated with subsequent memory on Day 1 and with successful long-term retention on Day 7. A representational similarity analysis in this parietal region revealed that beneficial recurrent retrieval was associated with representational variability, such that the pattern similarity on Day 1 was lower for retrieved words subsequently remembered compared with those subsequently forgot- ten. This was mirrored by a monotonically decreased BOLD signal change in dorsolateral prefrontal cortex on Day 1 as a function of repeated successful retrieval for words subsequently remembered, but not for words subsequently forgotten. This reduction in prefrontal response could reflect reduced demands on cognitive control. Collectively, the results offer novel insights into why memory retention benefits from repeated retrieval, and they suggest fundamental differences between repeated study and repeated testing. 

  • 128.
    Kauppi, Karolina
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Nilsson, Lars-Göran
    Adolfsson, Rolf
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Combined gene effects on hippocampal mnemonic processing: a large-scale imaging-genetics study of APOE, BDNF, KIBRA, and CLSTN22013In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 25, no Suppl., p. S140-S141Article in journal (Other academic)
  • 129.
    Klement, Göran
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Druzin, Michael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Haage, David
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Malinina, Evgenya
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Århem, Peter
    Karolinska Institute.
    Johansson, Staffan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Spontaneous ryanodine-receptor-dependent Ca2+-activated K+ currents and hyperpolarizations in rat medial preoptic neurons2010In: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 103, no 5, p. 2900-2911Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to clarify the identity of slow spontaneous currents, the underlying mechanism and possible role for impulse generation in neurons of the rat medial preoptic nucleus (MPN). Acutely dissociated neurons were studied with the perforated patch-clamp technique. Spontaneous outward currents, at a frequency of approximately 0.5 Hz and with a decay time constant of approximately 200 ms, were frequently detected in neurons when voltage-clamped between approximately -70 and -30 mV. The dependence on extracellular K(+) concentration was consistent with K(+) as the main charge carrier. We concluded that the main characteristics were similar to those of spontaneous miniature outward currents (SMOCs), previously reported mainly for muscle fibers and peripheral nerve. From the dependence on voltage and from a pharmacological analysis, we concluded that the currents were carried through small-conductance Ca(2+)-activated (SK) channels, of the SK3 subtype. From experiments with ryanodine, xestospongin C, and caffeine, we concluded that the spontaneous currents were triggered by Ca(2+) release from intracellular stores via ryanodine receptor channels. An apparent voltage dependence was explained by masking of the spontaneous currents as a consequence of steady SK-channel activation at membrane potentials > -30 mV. Under current-clamp conditions, corresponding transient hyperpolarizations occasionally exceeded 10 mV in amplitude and reduced the frequency of spontaneous impulses. In conclusion, MPN neurons display spontaneous hyperpolarizations triggered by Ca(2+) release via ryanodine receptors and SK3-channel activation. Thus such events may affect impulse firing of MPN neurons.

  • 130. Koch, Bo L.
    et al.
    Edvinsson, Åsa A.
    Koskinen, Lars-Owe D.
    University Hospital of Northern Sweden, Department of Neurosurgery, SE‐901 85 Umeå, Sweden.
    Inhalation of substance P and thiorphan: acute toxicity and effects on respiration in conscious guinea pigs.1999In: Journal of Applied Toxicology, ISSN 0260-437X, E-ISSN 1099-1263, Vol. 19, no 1, p. 19-23Article in journal (Refereed)
    Abstract [en]

    Substance P is a tachykinin and a biologically active neuropeptide. The peptide produces salivation, neuronal excitation, vasodilatation, increased vascular permeability and contraction of smooth muscles in the respiratory tract. The study was designed to evaluate the acute effects in guinea pigs of inhaled aerosolized Substance P (SP). Apart from the acute toxic effect of the peptide, the distribution in different organs was also investigated. The acute inhalation toxicity of SP (LC50, 15 min) when co-administrated with the neutral endopeptidase inhibitor thiorphan was 368 microg m(-3). The peptide caused an increase in respiratory rate proceeding a decrease in tidal volume. As the exposure proceeded, a decrease in both respiratory rate and further decreases in tidal volume were observed until either the animal died or the exposure was terminated. The decreases in respiratory rate and tidal volume were probably due to bronchoconstriction caused by SP. Eighteen per cent of the inhaled amount of radioactive SP was retained in the body, and the highest concentrations of radioactivity were found in the kidney, lung and liver. Substance P in combination with thiorphan administered as an aerosol is extremely toxic and highly potent. Exposure to the substance at extremely low air concentrations may result in incapacitation in humans.

  • 131.
    Kokinovic, Bojana
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. epartment of Neuroscience and Brain Technologies (NBT), Italian Institute of Technology (IIT), Genova, Italy.
    Medini, Paolo
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Loss of GABAB-mediated interhemispheric synaptic inhibition in stroke periphery2018In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 596, no 10, p. 1949-1964Article in journal (Refereed)
    Abstract [en]

    Recovery after stroke is mediated by plastic changes largely occurring in the lesion periphery. However, little is known about the microcircuit changes underlying recovery, the extent to which perilesional plasticity occurs at synaptic input vs. spike output level, and the connectivity behind such synaptic plasticity. We combined intrinsic imaging with extracellular and intracellular recordings and pharmacological inactivation in a focal stroke in mouse somatosensory cortex (S1). In vivo whole-cell recordings in hindlimb S1 (hS1) showed synaptic responses also to forelimb stimulation in controls, and such responses were abolished by stroke in the neighbouring forelimb area (fS1), suggesting that, under normal conditions, they originate via horizontal connections from the neighbouring fS1. Synaptic and spike responses to forelimb stimulation in hS1 recovered to quasi-normal levels 2weeks after stroke, without changes in intrinsic excitability and hindlimb-evoked spike responses. Recovered synaptic responses had longer latencies, suggesting a long-range origin of the recovery, prompting us to investigate the role of callosal inputs in the recovery process. Contralesional S1 silencing unmasked significantly larger responses to both limbs in controls, a phenomenon that was not observed when GABAB receptors were antagonized in the recorded area. Conversely, such GABAB-mediated interhemispheric inhibition was not detectable after stroke: callosal input silencing failed to change hindlimb responses, whereas it robustly reduced recovered forelimb responses. Thus, recovery of subthreshold responsiveness in the stroke periphery is accompanied by a loss of interhemispheric inhibition and this is a result of pathway-specific facilitatory action on the affected sensory response from the contralateral cortex.

  • 132.
    Kompus, Kristiina
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    How the past becomes present: neural mechanisms governing retrieval from episodic memory2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Remembering previously experienced events can happen as a result of an effortful retrieval attempt. At other occasions, a memory can enter our minds without any apparent effort – or, indeed, intention - to retrieve. Although it has long been appreciated that retrieval from episodic memory is intertwined with cognitive control, the neural mechanisms of memory-control interactions remain unclear.

    In this thesis I have used functional magnetic resonance imaging (fMRI) and scalp-recorded event-related potentials (ERP) to study the neural basis of episodic retrieval at varying levels of cognitive control. The dorsolateral prefrontal cortex (dlPFC) has been suggested to support a cognitive control mechanism (context processing) which is relevant during various situations that demand maintenance of current goals and rules. Although increased dlPFC recruitment with increasing context processing demands has been demonstrated during episodic retrieval, there are relatively few studies directly comparing the engagement of dlPFC during episodic retrieval with that during other task domains.

    In Study I, context processing demands were amplified in episodic retrieval, auditory attention and emotion regulation tasks. This led to overlapping dlPFC recruitment in the first two domains and a divergent reliance on ventromedial prefrontal cortex in the emotion domain. Thus, when selection between competing representations needs to be carried out in accordance with the currently relevant goals and task rules, the episodic memory system interacts with domain-general cognitive control mechanisms.

    Studies II and III explored the reactive nature of retrieval-specific control mechanisms: can we flexibly switch between semantic and episodic retrieval based on the information extracted from a retrieval cue? This was studied using a recognition memory task where the relevant information could with equal probability be supplied by the semantic or the episodic memory system. The fMRI results (Study II) showed that the brain activation during the ‘episodic’ but not the ‘semantic’ trials was expressed in the right prefrontal cortex. As the order of trials was unpredictable, the corresponding changes in brain activation might be evoked by differences in early cue-trace interactions. An event-related potential study (Study III) with the same experimental protocol as in Study II showed that neural processing corresponding to the two trial types diverged as early as in the time window 100-140 ms post-cue onset, thus highlighting the importance of early cue-trace matching in the selection of further retrieval processing.

    Study IV explored incidental episodic retrieval. Although this form of retrieval is a common experience in everyday life and a disturbing symptom in some psychiatric conditions, it is not clear how such spontaneous expressions of memory are initiated and to what extent the prefrontal cortex is engaged. The fMRI results showed, consistent with Study I, that dlPFC is specifically associated with the intention to retrieve, independently of success. Retrieval success engaged similar networks for incidentally as well as intentionally retrieved memories, comprising the hippocampus, precuneus, ventrolateral PFC, and the anterior cingulate cortex. Collectively, the fMRI and ERP results indicated that incidental retrieval was initiated by early (< 200 ms) oldness estimation carried out on the semantic information extracted from the retrieval cues.

    Taken together, the results of this thesis indicate that episodic retrieval can be initiated via two routes:  a bottom-up input rising early during the cue processing, and a top-down input provided by the cognitive control processes mediated by the prefrontal cortex.

  • 133.
    Kompus, Kristiina
    et al.
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Eichele, Tom
    University of Bergen.
    Hugdahl, Kenneth
    University of Bergen.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Radiation Sciences, Diagnostic Radiology.
    Early analysis of retrieval cues guides selection of retrieval processingManuscript (preprint) (Other academic)
    Abstract [en]

    Human long-term memory holds semantic and episodic memories. Retrieval from these two memory systems occurs independently. As required information may be held in either of these systems, the question arises how and when is the choice of retrieval processing (episodic/semantic) determined. Here we report results from an ERP study on healthy young adults during a forced-choice associative recognition task, designed to test the hypothesis that early processing of retrieval cues influences subsequent retrieval processing. The test items had previously been encoded repeatedly (6x) or only once (1x) during pre-experimental training period, thereby influencing the reliance on semantic or episodic retrieval processes.  Differences between the two conditions were observed for the familiarity-sensitive FN400 component as well as for a late (>1000 ms) component indexing post-retrieval processing. Most critically, we found that a difference between successfully retrieved 6x and 1x items emerged already during the 100-140 ms time window. These results indicate that choice of retrieval processes (episodic/semantic) depends on early matching between retrieval cues and memory traces.

  • 134.
    Kompus, Kristiina
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Eichele, Tom
    University of Bergen.
    Hugdahl, Kenneth
    University of Bergen.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology. Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Multimodal imaging of incidental retrieval: the low route to memory2011In: Journal of cognitive neuroscience, ISSN 0898-929X, E-ISSN 1530-8898, Vol. 23, no 4, p. 947-960Article in journal (Refereed)
    Abstract [en]

    Memories of past episodes frequently come to mind incidentally, without directed search. It has remained unclear how incidental retrieval processes are initiated in the brain. Here we used fMRI and ERP recordings to find brain activity that specifically correlates with incidental retrieval, as compared to intentional retrieval. Intentional retrieval was associated with increased activation in the dorsolateral prefrontal cortex. By contrast, incidental retrieval was associated with a reduced fMRI signal in posterior brain regions, including extrastriate and parahippocampal cortex, and a modulation of a posterior ERP component 170 ms after the onset of visual retrieval cues. Successful retrieval under both intentional and incidental conditions was associated with increased activation in hippocampus, precuneus and ventrolateral prefrontal cortex, as well as increased amplitude of the P600 ERP component. These results demonstrate how early bottom-up signals from the posterior cortex can lead to reactivation of episodic memories in the absence of strategic retrieval attempts.

  • 135.
    Korpos, E.
    et al.
    Institute of Physiological Chemistry, University of Muenster, Muenster, Germany.
    Kadri, N.
    Goeteborg University, Goeteborg, Sweden.
    Holmberg, D.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Cardell, S.
    Goeteborg University, Goeteborg, Sweden.
    Sorokin, L.
    Institute of Physiological Chemistry, University of Muenster, Muenster, Germany.
    The Role of the Extracellular Matrix in Leukocyte Infiltration into the Pancreas of Non Obese Diabetic Mice2011In: European Society for Microcirculation (ESM): German Society of Microcirculation and Vascular Biology (GfMVB)Munich, Germany, Berlin: Karger , 2011, Vol. 48, p. 334-334Conference paper (Refereed)
  • 136.
    Koskinen, Lars-Owe D.
    Department of Physiology and Medical Biophysics, Biomedical Centre University of Uppsala, Box 572, S-75123 Uppsala, Sweden.
    Cerebral and peripheral blood flow effects of TRH in the rat: a role of vagal nerves1989In: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 10, no 5, p. 933-938Article in journal (Refereed)
    Abstract [en]

    The cardiovascular effects of the IV infusion of TRH were studied in the rat. TRH tended to increase the MAP and markedly increased the CBF(tot) in the control group, in vagotomized animals and in methylatropine-pretreated rats. A marked vasodilation was noted in the pancreas, gastric mucosa, duodenum and cardiac muscle. This effect was turned to vasoconstriction, the heart excluded, in vagotomized animals. Muscarinic blockade attenuated the vasodilating effect of TRH in the duodenum and gastric mucosa. The results indicate that TRH elicits cerebral vasodilation and a partly nonmuscarinic parasympathetically mediated vasodilation in several gastrointestinal organs in parallel with a vasoconstriction which is unmasked by vagotomy.

  • 137.
    Koskinen, Lars-Owe D.
    Department of Physiology and Medical Biophysics, Biomedical Centre, University of Uppsala, Uppsala, Sweden.
    Effect of low intravenous doses of TRH, acid-TRH and cyclo(His-Pro) on cerebral and peripheral blood flows.1986In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 87, no 3, p. 509-519Article in journal (Refereed)
    Abstract [en]

    Local cerebral and peripheral blood flow in conscious and anaesthetized rabbits were investigated with the microsphere method, before and after the i.v. administration of 25 or 50 micrograms kg-1 thyrotropin-releasing hormone (TRH). Before the experiment, the cervical sympathetic chain was sectioned on one side in order to evaluate the possible effect of the sympathetic nerves on cranial and extracranial blood flows. Blood flow was also determined in anaesthetized rabbits before and after the administration of the TRH metabolites cyclo(His-Pro) and acid-TRH and after subsequent administration of 50 micrograms kg-1 TRH. TRH caused an increase in mean arterial blood pressure (MAP) of about 1 to 2 kPa whereas cyclo(His-Pro) and acid-TRH had no effect on MAP. In the anaesthetized animal an increase in total cerebral blood flow (CBFtot), from 71 +/- 7 to 107 +/- 12 g min-1 100 g-1 (P less than 0.05) was observed on the sympathetic intact side after 25 micrograms kg-1 TRH and a further increase to 130 +/- 9 g min-1 100g-1 (P less than 0.01) after 50 micrograms kg-1 TRH. A similar effect was observed on the sympathotomized side. An effect on CBF in the conscious animal was not detected. The control CBFtot (104 +/- 8 g min-1 100g-1) was higher in these animals than in the anaesthetized animals (P less than 0.02). Neither cyclo(His-Pro) nor acid-TRH mimicked the effect of TRH on CBF. In several peripheral tissues, e.g. skin, pancreas and gastric mucosa, a reduction in blood flow was noted after the administration of TRH in both anaesthetized and conscious rabbits. It was concluded that TRH can induce cerebral vasodilatation in animals with a depressed CBF, whereas the vasoconstrictor effect of TRH in peripheral organs is not markedly affected by the state of consciousness.

  • 138.
    Koskinen, Lars-Owe D.
    Department of Physiology and Medical Biophysics, Biomedical Centre, University of Uppsala, Uppsala, Sweden..
    Effects of raised intracranial pressure on regional cerebral blood flow: a comparison of effects of naloxone and TRH on the microcirculation in partial cerebral ischaemia.1985In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 85, no 2, p. 489-497Article in journal (Refereed)
    Abstract [en]

    The effects on regional cerebral blood flow (rCBF) of raised intracranial pressure (ICP) and of naloxone and thyrotropin releasing hormone (TRH) during this condition were studied in anaesthetized rabbits. The ICP was elevated until a central ischaemic response was observed. The regional blood flow was determined with the microsphere technique before and during elevation of the ICP (ICPe) and after drug treatment. Total CBF was reduced by about 70% during ICPe while the uveal blood flow increased slightly and some other peripheral tissue blood flows remained unaffected. The administration of TRH caused an increase in mean arterial blood pressure (MAP) from 11.9 +/- 0.6 to 14.6 +/- 0.7 kPa and a normalization of the rCBF. In some peripheral tissues, e.g. gastric mucosa and spleen, TRH reduced the blood flow by 53% and 76%, respectively. In blood pressure stabilized animals no effect on rCBF was seen after TRH. Naloxone had no consistent effect on MAP or local blood flow. It was concluded that in the range of cerebral perfusion pressure studied there was a passive relationship between cerebral blood flow and perfusion pressure. The lack of effect of naloxone and the marked effect of TRH during cerebral ischaemia are consistent with a mechanism of action of TRH not related to a 'physiological' antagonism of opioids.

  • 139.
    Koskinen, Lars-Owe D.
    Department of Physiology and Medical Biophysics Biomedical Center University of Uppsala S‐751 23 Uppsala, Sweden.
    Effects of TRH on blood flow and the microcirculation.1989In: Annals of the New York Academy of Sciences, ISSN 0077-8923, E-ISSN 1749-6632, Vol. 553, p. 353-69Article in journal (Refereed)
  • 140.
    Koskinen, Lars-Owe D.
    Department of Physiology and Medical Biophysics, Biomedical Centre, University of Uppsala, Sweden.
    Effects of TRH on cerebral and peripheral blood flows; role of submesencephalic brain stem centres.1986In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 128, no 2, p. 277-288Article in journal (Refereed)
    Abstract [en]

    The localization of the origin of the cardiovascular effects elicited by thyrotropin-releasing hormone (TRH) was attempted in this study. The radioactively labelled microsphere method was employed for measurement of regional cerebral (rCBF) and peripheral blood flow in albino rabbits anaesthetized with urethane. The effect of 50 micrograms and 2 mg kg-1 TRH (administered i.v.) on rCBF and peripheral blood flow was evaluated in animals with the brain stem sectioned (BSS) at the level of pons-mesencephalon. The cerebral vasodilating effect of TRH was abolished or attenuated, while the peripheral vasoconstriction and increase in mean arterial blood pressure (MAP) was unaffected. Cordotomy at the CI level caused a marked fall in MAP and abolished the pressor response to TRH. In animals infused with angiotensin II, in order to normalize the decreased MAP after cordotomy, TRH caused a marked increase in rCBF. Administration of 50 ng and 5 micrograms TRH into the fourth ventricle caused a marked peripheral vasoconstriction and pressor response. The same amounts of TRH administered into the mesencephalic aqueduct caused a marked increase in rCBF and peripheral vasoconstriction. The results indicate that TRH elicits the pressor and peripheral vasoconstrictor responses from a submesencephalic brain stem region. The increase in rCBF caused by TRH is probably mediated by a somewhat higher submesencephalic level.

  • 141.
    Koskinen, Lars-Owe D.
    Department of Neurosurgery, University Hospital, S-90185 Umeå, Sweden; Department of Physiology and Medical Biophysics, Biomedical Center University of Uppsala, Box 572, S-75123 Uppsala, Sweden.
    Naloxone and TRH affect regional blood flows in the anesthetized rabbit.1991In: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 12, no 6, p. 1273-1277Article in journal (Refereed)
    Abstract [en]

    The cardiovascular effects of IV naloxone and a subsequent administration of TRH IV were studied in the rabbit. Naloxone caused a vasodilation in the myocardium and adrenal glands. Naloxone elicited an increment in cerebral blood flow in several regions which attenuated the cerebrovasodilating effect of TRH in a few regions. The blockade of endogenous opioids with naloxone did not modify the peripheral vasoconstricting effect of TRH or affect the vascular effects of TRH mediated by the peripheral sympathetic nerves. The results indicate that naloxone has a vasodilating effect in the myocardium and CNS in anesthetized rabbits. The major part of the cardiovascular effect of TRH is not dependent on mechanisms sensitive to naloxone.

  • 142.
    Koskinen, Lars-Owe D.
    Department of Physiology and Medical Biophysics, Biomedical Centre, University of Uppsala, Uppsala, Sweden.
    The influence of bilateral electrical preganglionic sympathetic stimulation on intra- and extracranial blood flow.1987In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 92, no 2, p. 185-192Article in journal (Refereed)
    Abstract [en]

    The effects of bilateral electrical stimulation (SS) of the cervical sympathetic chain on intra- and extra cerebral blood flows were studied with the labelled microsphere method in the rabbit. Control blood flow was determined before the SS was started. The stimulation frequency was 7 Hz, the impulse duration 2 ms, the intensity 7 V and the stimulation time varied between 1 to 5 minutes before the second blood flow determination. Arterial blood gas values and blood pressure were unaffected by the stimulation. Due to the SS there were blood flow decrements in the extracranial tissues between 60-96%. The blood flow in the eyes, the dura, pineal gland and choroid plexa was markedly reduced during the SS. No obvious effect was elicited by the SS in the regional or total cerebral blood flow. The stimulation to control blood flow ratio ranged between 0.92 +/- 0.08 to 1.13 +/- 0.09 in different parts of the brain. The conclusions are that SS elicits vasoconstriction in several extra- and intracranial nonneuronal tissues and in the eye. Cerebral blood flow is not influenced by the SS.

  • 143.
    Koskinen, Lars-Owe D.
    Department of Physiology and Medical Biophysics, Biomedical Centre, University of Uppsala; Department of Neurosurgery, University Hospital, Umeå; Department of Biomedicine, National Defence Research Establishment, Umeå, Sweden.
    The influence of muscarinic and prostaglandic mechanisms on regional cerebral and peripheral blood flows and on the vascular effects of thyrotropin releasing hormone (TRH).1994In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 152, no 4, p. 399-406Article in journal (Refereed)
    Abstract [en]

    TRH has pronounced vascular effects. The final transmitter mechanisms of these effects are not fully understood. The present study was conducted in order to elucidate whether these effects are mediated by prostaglandic or muscarinic mechanisms. Muscarinic blockade augmented the vasoconstricting- and pressor effect of TRH; vasodilation in the brain was attenuated only in the caudate nucleus. Indomethacin provoked a decrease in regional cerebral blood flow and in the gastric mucosal blood flow. No effect of indomethacin was observed on the vascular effects of TRH. It is concluded that the cerebral vasodilating and peripheral vasoconstricting effects of TRH are not mediated by prostaglandins. Muscarinic mechanisms are involved in the vasodilating effect of TRH only in the caudate nucleus.

  • 144.
    Koskinen, Lars-Owe D.
    et al.
    Department of Physiology and Medical Biophysics, Biomedical Center, University of Uppsala, Sweden.
    Bill, Anders
    Department of Physiology and Medical Biophysics, Biomedical Center, University of Uppsala, Sweden.
    Regional cerebral, ocular and peripheral vascular effects of naloxone and morphine in unanesthetized rabbits.1983In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 119, no 3, p. 235-241Article in journal (Refereed)
    Abstract [en]

    Effects of morphine and naloxone were investigated on cerebral, ocular and peripheral blood flow in unanesthetized rabbits. Blood flow measurements were performed with the labelled microsphere method. Cervical sympathotomy was performed on one side the day before the flow determination. Naloxone 2 mg/kg b.w. i.v. had no consistent effect on cerebral, ocular or peripheral blood flow or on mean arterial blood pressure. Morphine 2 mg/kg b.w. i.v. caused a rise in PaCO2 of 0.9 kPa and tended to increase cerebral blood flow in all parts investigated. In the hippocampal region, caudate nucleus and collicles the increase in flow was about 30% which is more than expected from the rise in PaCO2. Blood flow in the retina increased while the other parts of the eye showed no consistent changes in blood flow. Morphine reduced the blood flow in the duodenum by 60%. Mean arterial blood pressure did not change after morphine. No effect of the cervical sympathotomy was detected on cerebral or ocular blood flow before or after morphine or naloxone. Thus, we found no evidence for a tonically operating opioid system controlling cerebral, ocular or peripheral blood flow. However, exogenously administrated opiate can influence blood flows in these areas.

  • 145.
    Koskinen, Lars-Owe D.
    et al.
    Department of Physiology and Medical Biophysics, Biomedical Center, University of Uppsala, Sweden.
    Bill, Anders
    Department of Physiology and Medical Biophysics, Biomedical Center, University of Uppsala, Sweden.
    Thyrotropin-releasing hormone (TRH) causes sympathetic activation and cerebral vasodilation in the rabbit.1984In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 122, no 2, p. 127-136Article in journal (Refereed)
    Abstract [en]

    The effects of TRH on regional blood flow were studied in rabbits under urethane anesthesia. Four types of experiments were performed with the following results. (1) I.v. injection of 2 mg/kg b.w. TRH in animals with unilateral cervical sympathotomy caused a rise in mean arterial blood pressure from 10.0 +/- 0.5 to 13.3 +/- 0.5 kPa. Total cerebral blood flow, measured with labeled microspheres, increased from 75 +/- 5 to 126 +/- 16 g/min/100 g tissue on the intact side. There was a similar increase on the side with sympathotomy. The greatest increase, about 70%, was observed in cortical gray matter, caudate nucleus and thalamic region. There were marked reductions in blood flows in the spleen, gastric mucosa, skin and skeletal muscle. Mydriasis occurred on the side with an intact sympathetic supply. (2) I.v. infusion of 0.06 mg/kg b.w. per min TRH in animals with unilateral cervical sympathotomy and stabilized blood pressure increased total cerebral blood flow from 84 +/- 10 to 139 +/- 7 g/min/100 g. Blood flows to the masseter muscle, submandibular gland and facial skin but not to the eye or tongue were markedly reduced on the side with an intact sympathetic supply while little or no effect was observed on the side with sympathotomy. (3) Unilateral peripheral stimulation of the sympathetic chain at 1 Hz after bilateral sympathotomy caused a reduction in blood flows in the tongue, masseter muscle, submandibular gland and facial skin in animals with stabilized blood pressure. No potentiation of the stimulation effect was observed during TRH infusion. (4) The arteriovenous difference in oxygen saturation in the brain decreased from 39.1 +/- 2.8 to 26.4 +/- 3.7% after i.v. injection of 2 mg/kg b.w. TRH. The results indicate that TRH caused cerebral vasodilation in excess of that required by possible changes in cerebral metabolism. The vasoconstriction in the head region and the mydriasis was caused mainly by an increase in the activity of the cervical sympathetic nerves.

  • 146.
    Koskinen, Lars-Owe D.
    et al.
    Department of Biomedicine, Defense Research Establishment, Umeå, Sweden. Department of Neurosurgery, Umeå University Hospital, Umeå, Sweden.
    Koch, Mona L.
    Puu, Gertrud
    The neuropeptide TRH has a minor effect on the enzymatic activity of acetylcholinesterase in vitro.1998In: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 19, no 10, p. 1675-1677Article in journal (Refereed)
    Abstract [en]

    The neuropeptide thyrotropin-releasing hormone (TRH) elicits a variety of physiological effects of which some are due to cholinergic mechanisms. TRH modulates in vivo the effects of compounds affecting acetylcholinesterase (AChE). In the present study the in vitro effects of TRH on the activity of AChE were explored. TRH has no effect at physiologically relevant concentrations. At unphysiologically high concentrations (>5 mM) a slight inhibition was found. This was noticed also when the enzyme was exposed to the amide-free tripeptide analog p-Glu-His-Pro. We conclude that any cholinergic effect of TRH observed in vivo is unlikely to be due to a direct interaction of the peptide with AChE.

  • 147.
    Larsson, Jan
    et al.
    Umeå University. Department of Pharmacology, Umeå University, S-901 87 Umeå, Sweden.
    Koskinen, Lars-Owe D.
    Department of Neurosurgery, University Hospital, S-901 85 Umeå, Sweden; Division of Biomedicine, Department of NBC Defence, National Defence Research Establishment, S-901 82 Umeå, Sweden.
    Wahlström, Göran
    Umeå University.
    Effects of TRH and atropine on induction and duration of anesthesia with propofol in rats.1996In: Peptides, ISSN 0196-9781, E-ISSN 1873-5169, Vol. 17, no 2, p. 293-297Article in journal (Refereed)
    Abstract [en]

    The effects of IV TRH pretreatment on induction of anesthesia with propofol or pentobarbital were investigated in rats. The effects of IV TRH, administered after induction, on duration of propofol anesthesia and the interaction with atropine were also studied. The doses of propofol or pentobarbital were not influenced by TRH. TRH reduced duration of anesthesia after propofol, with higher brain concentrations of propofol at recovery. Atropine did not block this effect, but given alone prolonged duration of anesthesia. It is concluded that TRH shortens the duration of propofol anesthesia, probably due to a pharmacodynamic effect and not to a pharmacokinetic interaction.

  • 148. Lawley, Justin S.
    et al.
    Levine, Benjamin D.
    Williams, Michael A.
    Malm, Jan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Eklund, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Polaner, David M.
    Subudhi, Andrew W.
    Hackett, Peter H.
    Roach, Robert C.
    Cerebral spinal fluid dynamics: effect of hypoxia and implications for high-altitude illness2016In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 120, no 2, p. 251-262Article, review/survey (Refereed)
    Abstract [en]

    The pathophysiology of acute mountain sickness and high-altitude cerebral edema, the cerebral forms of high-altitude illness, remain uncertain and controversial. Persistently elevated or pathological fluctuations in intracranial pressure are thought to cause symptoms similar to those reported by individuals suffering cerebral forms of high-altitude illness. This review first focuses on the basic physiology of the craniospinal system, including a detailed discussion of the long-term and dynamic regulation of intracranial pressure. Thereafter, we critically examine the available literature, based primarily on invasive pressure monitoring, that suggests intracranial pressure is acutely elevated at altitude due to brain swelling and/or elevated sagittal sinus pressure, but normalizes over time. We hypothesize that fluctuations in intracranial pressure occur around a slightly elevated or normal mean intracranial pressure, in conjunction with oscillations in arterial PO2 and arterial blood pressure. Then these modest fluctuations in intracranial pressure, in concert with direct vascular stretch due to dilatation and/or increased blood pressure transmission, activate the trigeminal vascular system and cause symptoms of acute mountain sickness. Elevated brain water (vasogenic edema) may be due to breakdown of the blood-brain barrier. However, new information suggests cerebral spinal fluid flux into the brain may be an important factor. Regardless of the source (or mechanisms responsible) for the excess brain water, brain swelling occurs, and a "tight fit" brain would be a major risk factor to produce symptoms; activities that produce large changes in brain volume and cause fluctuations in blood pressure are likely contributing factors.

  • 149. 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)
  • 150. Lindberg, F
    et al.
    Öhberg, Fredrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Brodin, LA
    Grönlund, Christer
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Assessment of intramuscular activation patterns using ultrasound M-mode strain2013In: Journal of Electromyography & Kinesiology, ISSN 1050-6411, E-ISSN 1873-5711, Vol. 23, no 4, p. 879-885Article in journal (Refereed)
    Abstract [en]

    The intramuscular activation pattern can be connected to the motor unit recruitment strategy of force generation and fatigue resistance. Electromyography has earlier been used in several studies to quantify the spatial inhomogeneity of the muscle activation. We applied ultrasound M-mode strain to study the activation pattern through the tissue deformation. Correlation values of the strain at different force levels were used to quantify the spatial changes in the activation. The assessment was done including the biceps brachii muscle of 8 healthy subjects performing isometric elbow flexion contractions ranging from 0% to 80% of maximum voluntary contraction. The obtained results were repeatable and demonstrated consistent changes of the correlation values during force regulation, in agreement with previously presented EMG-results. Both intra-subject and inter-subject activation patterns of strain were considered along and transverse the fiber direction. The results suggest that ultrasound M-mode strain can be used as a complementary method to study intramuscular activation patterns with high spatial resolution.

    (C) 2013 Elsevier Ltd. All rights reserved.

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