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  • 1.
    Ahlén, Caroline
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Outcome of patients with severe aortic stenosis – A retrospective follow-up study2008Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Aortic stenosis is the most common valvular disease in the adult population. A significant aortic stenosis is a serious condition, and if a symptomatic patient is not operated on, it may in most cases cause death. We have examined how many aortic stenoses that were diagnosed during one year, and a follow-up of the patients was also performed. We found 77 patients with significant aortic stenosis with a mean age of 76±13 years. At the time of follow-up 30 (39%) patients, aged between 29-85 years, had been surgically treated with implantation of a valve prosthesis within 2-23 months after the initial examination. At this initial examination 14 of the 30 patients who later underwent surgery had no symptoms. A coronary bypass operation was also performed on seven patients. Postoperative complications were observed in six patients, but none of them was fatal. At the initial examinations there were 26 (34%) patients with a significant aortic stenosis and symptoms who were not treated surgically. The main reason why these patients were not operated was high age, unwillingness, or severe left ventricular dysfunction. This study indicates the importance of repeated clinical and echocardiograpic examinations in patients with aortic stenosis. Almost half of the patients, that later underwent surgery, had no symptoms at the initial examination, but later developed symptoms which made surgery necessary. In one third of the patients no surgery was performed in spite of clinical symptoms.

  • 2. Alfonso, Julieta
    et al.
    Pollevick, Guido
    Castensson, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Jazin, Elena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Frasch, Alberto
    Analysis of gene expression in the rat hippocampus using Real Time PCR reveals high inter-individual variation in mRNA expression levels2002In: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547, Vol. 67, no 2, p. 225-34Article in journal (Refereed)
    Abstract [en]

    In mammals, gene transcription is a step subjected to tight regulation mechanisms. In fact, changes in mRNA levels in the central nervous system (CNS) can account for numerous phenotypic differences in brain function. We performed a high-resolution analysis of mRNA expression levels for 37 genes selected from a normal rat hippocampus cDNA library. mRNA amounts were quantified using a Real Time PCR SYBR Green assay. We found that, in general, individuals from an inbred rat population (n = 20) have shown 2-3 times differences in the basal level of expression of the genes analyzed. Up to several fold differences among individuals were observed for certain genes. These inter-individual differences were obtained after correction for the different amounts of mRNA in each sample. Power calculations were performed to determine the number of individuals required to detect reliable differences in expression levels between a control and an experimental group. These data indicated that, depending on the variability of the candidate gene selected, it was necessary to analyze from five to 135 individuals in each group to detect differences of 50% in the levels of mRNA expression between two groups investigated. The comparison of mRNA abundance from different genes revealed a wide range of expression levels for the 37 genes, showing a 26,000-fold difference between the highest and lowest expressed gene.

  • 3.
    Almgren, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Endotracheal Suction a Reopened Problem2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    During mechanical ventilation, patients are connected to the ventilator by an endotracheal tube. The tube needs to be cleaned from mucus by suction, which can cause negative effects such as lung collapse, hypoxemia and desaturation. These can be avoided by preoxygenation, change of ventilator settings, use of closed suction systems and recruitment manoeuvres. The aim of the study was to investigate the effects of endotracheal suction during different ventilator settings and by different suction methods. A method to reverse side effects was investigated.

    In anaesthetized pigs, the effect of suction during volume and pressure-controlled ventilation was investigated, and the effect of different suction systems and catheter sizes were compared. Suction efficacy was investigated in a bench study. The effect of recruitment manoeuvre added after suction, i.e. post-suction recruitment manoeuvre was evaluated.

    Endotracheal suction causes lung volume loss leading to impaired gas exchange, an effect that is more severe in pressure-controlled ventilation than in volume-controlled ventilation. When 14 French suction catheters were used more side effects were found compared to 12 French catheters, but no difference was found between open and closed suction system in pressure-controlled ventilation. Open suction system was more effective to remove mucus compared to closed system. Post-suction recruitment manoeuvre restored the side effects after the first recruitment when it was applied directly after suction.

    In conclusion, open endotracheal suction causes impairment in gas exchange and lung mechanics, and more so in pressure-controlled than in volume-controlled mode. These changes can be minimized if smaller suction catheters are used. A post-suction recruitment manoeuvre applied directly after suction restores lung function. It is obvious that the recruitment manoeuvre should be added directly after suction, because if the manoeuvre is delayed and the lung is collapsed and left collapsed, it will be more difficult to recruit the lung.

    List of papers
    1. Side effects of endotracheal suction in pressure and volume controlled ventilation
    Open this publication in new window or tab >>Side effects of endotracheal suction in pressure and volume controlled ventilation
    2004 (English)In: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 125, no 3, p. 1077-1080Article in journal (Refereed) Published
    Abstract [en]

    STUDY OBJECTIVES:

    To investigate the effects of endotracheal suction in volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) with an open suction system (OSS) or a closed suction system (CSS).

    DESIGN:

    Randomized comparison.

    SETTING:

    Animal research laboratory.

    PATIENTS:

    Twelve healthy anesthetized pigs.

    INTERVENTIONS:

    The effects of endotracheal suction during VCV and PCV with tidal volume (VT) of 14 mL/kg were compared. A 60-mm inner-diameter endotracheal tube was used. Ten-second suction was performed using OSS and CSS with 12F and 14F catheters connected to - 14 kPa vacuum.

    MEASUREMENTS AND RESULTS:

    Thirty minutes after suction in PCV, VT was still decreased by 27% (p < 0.001), compliance (Crs) by 28% (p < 0.001), and PaO(2) by 26% (p < 0.001); PaCO(2) was increased by 42% (p < 0.0001) and venous admixture by 158% (p = 0.003). Suction in VCV affected only Crs (decreased by 23%, p < 0.001) and plateau pressure (increased by 24%, p < 0.001). The initial impairment of gas exchange following suction in VCV was no longer statistically significant after 30 min.

    CONCLUSIONS:

    In conclusion, endotracheal suction causes lung collapse leading to impaired gas exchange, an effect that is more severe and persistent in PCV than in VCV.

    Keywords
    Animals, Intubation; Intratracheal/*adverse effects, Lung Compliance, Pulmonary Gas Exchange, Respiration; Artificial/*methods, Suction/*adverse effects, Support; Non-U.S. Gov't, Swine, Tidal Volume
    National Category
    Physiology
    Identifiers
    urn:nbn:se:uu:diva-92641 (URN)10.1378/chest.125.3.1077 (DOI)15006972 (PubMedID)
    Available from: 2005-02-25 Created: 2005-02-25 Last updated: 2018-01-13Bibliographically approved
    2. Negative tracheal pressure during suction differs between suction systems and catheter sizes
    Open this publication in new window or tab >>Negative tracheal pressure during suction differs between suction systems and catheter sizes
    2005 (English)Article in journal (Refereed) Published
    Place, publisher, year, edition, pages
    Uppsala: Institutionen för medicinsk cellbiologi, 2005
    National Category
    Physiology
    Identifiers
    urn:nbn:se:uu:diva-7236 (URN)
    Available from: 2007-10-24 Created: 2007-10-24 Last updated: 2018-01-13
    3. Effectiveness and side effects of closed and open suctioning: an experimental evaluation
    Open this publication in new window or tab >>Effectiveness and side effects of closed and open suctioning: an experimental evaluation
    Show others...
    2004 In: Intensive Care Medicine, Vol. 30, no 8, p. 1630-7Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-92643 (URN)
    Available from: 2005-02-25 Created: 2005-02-25Bibliographically approved
    4. Post-suction recruitment manoeuvre restores lung function in healthy, anaesthetized pigs
    Open this publication in new window or tab >>Post-suction recruitment manoeuvre restores lung function in healthy, anaesthetized pigs
    2004 (English)In: Anaesthesia and Intensive Care, ISSN 0310-057X, E-ISSN 1448-0271, Vol. 32, no 3, p. 339-345Article in journal (Refereed) Published
    Abstract [en]

    Endotracheal suction can cause partial lung collapse and hypoxia and alter lung mechanics. We investigated the effects of adding a recruitment manoeuvre directly after endotracheal suction to restore lung volume in volume-controlled ventilation and pressure-controlled ventilation modes. Five anaesthetized pigs were investigated. The effects of endotracheal suction with or without a recruitment manoeuvre were compared in random order. In volume-controlled ventilation, compliance decreased after suction from 33 +/- 5 to 26 +/- 6 ml x cmH2O(-1) (P<0.05), and 30 minutes later it remained decreased at 25 +/- 6 ml x cmH2O(-1). Venous admixture increased after suction from 5 +/- 2 to 8 +/- 4% (P<0.05), but had recovered at 30 minutes. In pressure-controlled ventilation, compliance decreased after suction from 34 +/- 3 to 25 +/- 7 ml x cmH2O(-1) (P<0.05), and 30 minutes later it remained decreased at 25 +/- 7 ml x cmH2O(-1). Venous admixture increased after suction from 5 +/- 2 to 13 +/- 7% (P<0.05), and had not recovered after 30 minutes, 10 +/- 4%. When a recruitment manoeuvre was applied directly after suction, no negative side-effects were registered in volume-controlled ventilation or pressure-controlled ventilation. We conclude that the impairment of lung mechanics and gas exchange induced by endotracheal suction can be prevented by a simple post-suction recruitment manoeuvre. Further studies are needed to identify a suitable suction recruitment manoeuvre in patients with diseased lungs.

    National Category
    Physiology
    Identifiers
    urn:nbn:se:uu:diva-92644 (URN)15264727 (PubMedID)
    Available from: 2005-02-25 Created: 2005-02-25 Last updated: 2018-01-13Bibliographically approved
    5. The time frame for post-suction recruitment manoeuvre
    Open this publication in new window or tab >>The time frame for post-suction recruitment manoeuvre
    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:uu:diva-92645 (URN)
    Available from: 2005-02-25 Created: 2005-02-25 Last updated: 2010-01-13Bibliographically approved
  • 4.
    Almgren, Birgitta
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
    Strid, Niklas
    Wickerts, Carl-Johan
    Högman, Marieann
    Negative tracheal pressure during suction differs between suction systems and catheter sizes2005Article in journal (Refereed)
  • 5.
    Almgren, Birgitta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Wickerts, Carl-Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Heinonen, Erkki
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Högman, Marieann
    Side effects of endotracheal suction in pressure and volume controlled ventilation2004In: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 125, no 3, p. 1077-1080Article in journal (Refereed)
    Abstract [en]

    STUDY OBJECTIVES:

    To investigate the effects of endotracheal suction in volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) with an open suction system (OSS) or a closed suction system (CSS).

    DESIGN:

    Randomized comparison.

    SETTING:

    Animal research laboratory.

    PATIENTS:

    Twelve healthy anesthetized pigs.

    INTERVENTIONS:

    The effects of endotracheal suction during VCV and PCV with tidal volume (VT) of 14 mL/kg were compared. A 60-mm inner-diameter endotracheal tube was used. Ten-second suction was performed using OSS and CSS with 12F and 14F catheters connected to - 14 kPa vacuum.

    MEASUREMENTS AND RESULTS:

    Thirty minutes after suction in PCV, VT was still decreased by 27% (p < 0.001), compliance (Crs) by 28% (p < 0.001), and PaO(2) by 26% (p < 0.001); PaCO(2) was increased by 42% (p < 0.0001) and venous admixture by 158% (p = 0.003). Suction in VCV affected only Crs (decreased by 23%, p < 0.001) and plateau pressure (increased by 24%, p < 0.001). The initial impairment of gas exchange following suction in VCV was no longer statistically significant after 30 min.

    CONCLUSIONS:

    In conclusion, endotracheal suction causes lung collapse leading to impaired gas exchange, an effect that is more severe and persistent in PCV than in VCV.

  • 6.
    Almgren, Birgitta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Wickerts, Carl-Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Högman, Marieann
    Post-suction recruitment manoeuvre restores lung function in healthy, anaesthetized pigs2004In: Anaesthesia and Intensive Care, ISSN 0310-057X, E-ISSN 1448-0271, Vol. 32, no 3, p. 339-345Article in journal (Refereed)
    Abstract [en]

    Endotracheal suction can cause partial lung collapse and hypoxia and alter lung mechanics. We investigated the effects of adding a recruitment manoeuvre directly after endotracheal suction to restore lung volume in volume-controlled ventilation and pressure-controlled ventilation modes. Five anaesthetized pigs were investigated. The effects of endotracheal suction with or without a recruitment manoeuvre were compared in random order. In volume-controlled ventilation, compliance decreased after suction from 33 +/- 5 to 26 +/- 6 ml x cmH2O(-1) (P<0.05), and 30 minutes later it remained decreased at 25 +/- 6 ml x cmH2O(-1). Venous admixture increased after suction from 5 +/- 2 to 8 +/- 4% (P<0.05), but had recovered at 30 minutes. In pressure-controlled ventilation, compliance decreased after suction from 34 +/- 3 to 25 +/- 7 ml x cmH2O(-1) (P<0.05), and 30 minutes later it remained decreased at 25 +/- 7 ml x cmH2O(-1). Venous admixture increased after suction from 5 +/- 2 to 13 +/- 7% (P<0.05), and had not recovered after 30 minutes, 10 +/- 4%. When a recruitment manoeuvre was applied directly after suction, no negative side-effects were registered in volume-controlled ventilation or pressure-controlled ventilation. We conclude that the impairment of lung mechanics and gas exchange induced by endotracheal suction can be prevented by a simple post-suction recruitment manoeuvre. Further studies are needed to identify a suitable suction recruitment manoeuvre in patients with diseased lungs.

  • 7.
    Amandusson, Åsa
    et al.
    Division of Cell Biology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University.
    Blomqvist, Anders
    Estrogen receptor-α expression in nociceptive-responsive neurons in the medullary dorsal horn of the female rat2010In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149, Vol. 14, no 3, p. 245-248Article in journal (Refereed)
    Abstract [en]

    Estrogens exert a substantial influence on the transmission of nociceptive stimuli and the susceptibility to pain disorders as made evident by studies in both animals and human subjects. The estrogen receptor (ER) seems to be of crucial importance to the cellular mechanisms underlying such an influence. However, it has not been clarified whether nociceptive neurons activated by pain express ERs. In this study, a noxious injection of formalin was given into the lower lip of female rats, thereby activating nociceptive neurons in the trigeminal subnucleus caudalis as demonstrated by immunohistochemical labeling of Fos. Using a dual-label immunohistochemistry protocol ERalpha-containing cells were visualized in the same sections. In the superficial layers of the medullary dorsal horn, 12% of ERalpha-labeled cells, mainly located in lamina II, also expressed noxious-induced Fos. These findings show that nociceptive-responsive neurons in the medullary dorsal horn express ERalpha, thus providing a possible morphological basis for the hypothesis that estrogens directly regulate pain transmission at this level.

  • 8.
    Amandusson, Åsa
    et al.
    Linköpings Universitet.
    Hermansson, O
    Blomqvist, A
    Estrogen receptor-like immunoreactivity in the medullary and spinal dorsal horn of the female rat1995In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 196, no 1-2, p. 25-28Article in journal (Refereed)
    Abstract [en]

    Using an immunohistochemical technique, we demonstrate that large numbers of neurons in the laminar spinal trigeminal nucleus and spinal gray matter of the female rat express estrogen receptors (ER). Densely packed ER-immunoreactive neurons were present in lamina II, but labeled neurons were also present in lamina I, the neck of the dorsal horn, and in lamina X. Labeling was present throughout the length of the spinal cord, with the exception of segments caudal to S1, which were unlabeled. The distribution of ER-containing neurons to areas that are involved in processing of primary afferent nociceptive information suggests that the pain modulatory effects of estrogen may be exerted at the spinal level.

  • 9.
    Andersson, Arne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Department of Medical Cell Biology: Annual Report 20072008Collection (editor) (Other (popular science, discussion, etc.))
  • 10.
    Andersson, Arne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Department of Medical Cell Biology: Annual Report 20082009Collection (editor) (Other (popular science, discussion, etc.))
  • 11.
    Appelberg, Jonas
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Ventilation and Lung Volume During Sleep and in Obstructive Sleep Apnea2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Obstructive sleep apnea (OSA) appears to affect up to 5% of the population. The extent to what pulmonary function awake and during sleep relates to obstructive breathing and hypoxemia during sleep in these patients is unclear. The aim of this study was to investigate respiratory function in patients with varying degree of snoring and OSA and to analyse regional lung aeration during sleep.

    In all, 35 healthy subjects and 90 patients with snoring and OSA were studied. The ventilatory response to CO2 (VRCO2) was measured. Lung function tests were performed. A technique based on computed tomography was developed to study lung aeration during sleep.

    Patients with OSA displayed a higher VRCO2 in comparison to healthy subjects and snorers (p<0.01). Increased closing volume and reduced expiratory reserve volume (ERV) were found in patients with OSA (p<0.001). In a multiple regression analysis, ERV was an independent predictor of nocturnal apnea (R2=0.13; p=0.001) and desaturation frequency (R2=0.11; p<0.01). In both healthy subjects and OSA patients, lung aeration was reduced during sleep by 0.10 ml gas/g tissue in the dorsal lung region (p<0.05 and p<0.01). OSA patients had a significantly lower gas/tissue ratio in comparison to healthy subjects both awake (-23%; p<0.04) and during sleep (-25%; p<0.04). In a univariate analysis, functional residual capacity (FRC) correlated with the change in lung aeration from wakefulness to sleep (r=-0.78; p<0.001). In patients with OSA, ERV (r=-0.69; p<0.05) and sleep time (r=0.69; p<0.05) correlated with the fall in lung aeration.

    In conclusion, patients with OSA display an increased ventilatory response to CO2, reduced ERV and increased closing volume. ERV predicts nocturnal apnea and desaturation frequency to a similar extent as obesity. Lung aeration is reduced in the dorsal region during sleep and patients with OSA display a lower amount of gas in comparison to healthy subjects. Decrease in lung volumes, promoting airway closure, and loss of muscle tone contributed to the altered lung function during sleep.

    List of papers
    1. Ventilatory response to CO2 in patients with snoring, obstructive hypopnoea and obstructive apnoea
    Open this publication in new window or tab >>Ventilatory response to CO2 in patients with snoring, obstructive hypopnoea and obstructive apnoea
    1997 In: Clinical Physiology, Vol. 17, p. 497-507Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-90212 (URN)
    Available from: 2003-04-14 Created: 2003-04-14Bibliographically approved
    2. Lung volume and its correlation to nocturnal apnoea and desaturation
    Open this publication in new window or tab >>Lung volume and its correlation to nocturnal apnoea and desaturation
    2000 In: Respiratory Medicine, Vol. 94, p. 233-239Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-90213 (URN)
    Available from: 2003-04-14 Created: 2003-04-14Bibliographically approved
    3. Lung aeration during sleep
    Open this publication in new window or tab >>Lung aeration during sleep
    Show others...
    2007 (English)In: Chest, ISSN 0012-3692, E-ISSN 1931-3543, Vol. 131, no 1, p. 122-129Article in journal (Refereed) Published
    Abstract [en]

    Background: During sleep, ventilation and functional residual capacity (FRC) decrease slightly. This study addresses regional lung aeration during wakefulness and sleep. Methods: Ten healthy subjects underwent spirometry awake and with polysomnography, including pulse oximetry, and also CT when awake and during sleep. Lung aeration in different lung regions was analyzed. Another three subjects were studied awake to develop a protocol for dynamic CT scanning during breathing. Results: Aeration in the dorsal, dependent lung region decreased from a mean of 1.14 ± 0.34 mL (± SD) of gas per gram of lung tissue during wakefulness to 1.04 ± 0.29 mL/g during non-rapid eye movement (NREM) sleep (- 9%) [p = 0.034]. In contrast, aeration increased in the most ventral, nondependent lung region, from 3.52 ± 0.77 to 3.73 ± 0.83 mL/g (+ 6%) [p = 0.007]. In one subject studied during rapid eye movement (REM) sleep, aeration decreased from 0.84 to 0.65 mL/g (- 23%). The fall in dorsal lung aeration during sleep correlated to awake FRC (R2 = 0.60; p = 0.008). Airway closure, measured awake, occurred near and sometimes above the FRC level. Ventilation tended to be larger in dependent, dorsal lung regions, both awake and during sleep (upper region vs lower region, 3.8% vs 4.9% awake, p = 0.16, and 4.5% vs 5.5% asleep, p = 0.09, respectively). Conclusions: Aeration is reduced in dependent lung regions and increased in ventral regions during NREM and REM sleep. Ventilation was more uniformly distributed between upper and lower lung regions than has previously been reported in awake, upright subjects. Reduced respiratory muscle tone and airway closure are likely causative factors.

    Keywords
    Airway closure, anesthesia, CT, lung aeration, lung volume, sleep, ventilation
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-90214 (URN)10.1378/chest.06-0359 (DOI)000243548100020 ()17218565 (PubMedID)
    Available from: 2003-04-14 Created: 2003-04-14 Last updated: 2017-12-14Bibliographically approved
    4. Lung aeration during sleep in patients with obstructive sleep apnea
    Open this publication in new window or tab >>Lung aeration during sleep in patients with obstructive sleep apnea
    Show others...
    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:uu:diva-90215 (URN)
    Available from: 2003-04-14 Created: 2003-04-14 Last updated: 2010-01-13Bibliographically approved
  • 12.
    Atuma, C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Engstrand, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Physiology.
    Holm, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Physiology.
    Helicobacter pylori extracts reduce gastric mucosal blood flow by a nitric oxide-independent but mast cell- and platelet-activating factor receptor-dependent pathway in rats1999In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 34, no 12, p. 1183-1189Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We have previously shown that water extracts from Helicobacter pylori reduce gastric mucosal blood flow by approximately 15%. It has also been suggested that H. pylori can inhibit endogenous nitric oxide (NO) biosynthesis. Our aim was to examine whether the reduction in blood flow induced by H. pylori is the direct consequence of an NO synthase inhibition and the possible involvement of mast cell degranulation.

    METHODS: A water extract was produced from wildtype strain 88-23. The extract was applied on the exteriorized gastric corporal mucosa in inactin-anesthetized rats, after removing as much as possible of the mucus layer, during intravital microscopy. Blood flow was measured with laser-Doppler flowmetry.

    RESULTS: In rats pretreated with the NO synthase inhibitor N-nitro-L-arginine there was a 19% +/- 6% reduction in blood flow 40 min after application of the extract, and a 27% +/- 9% reduction after another 20 min with saline. The reduction was abolished by concomitant pretreatment with the mast cell stabilizer ketotifen or the platelet-activating factor (PAF) receptor antagonist WEB2086.

    CONCLUSION: The reduction in mucosal blood flow induced by the extract was probably mediated through an acute inflammatory response involving mast cell degranulation with consequent PAF secretion. The effect on blood flow was not the result of a decrease in vascular tone due to an inhibition of endogenous NO biosynthesis.

  • 13.
    Atuma, Christer
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Physiology.
    Gastrointestinal mucosal protective mechanisms: Mudolatory effects of Heliobacter pyroli on the gastric mucus gel barrier and mucosal blood flow in vivo2000Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The gastrointestinal mucus gel layer and blood flow are two important mechanisms for protection at the pre-epithelial and sub-epithelial levels, respectively. Helicobacter pylori might circumvent these mechanisms and elicit a chronic inflammatory response with consequent ulcers in the stomach and duodenum. In this thesis, the physical state and properties of the adherent mucus gel layer was studied from the stomach to colon. Furthermore, the acute and chronic effects of H. pylori on the integrity of the mucus gel layer and mucosal blood flow were studied in the anesthetized rat.

    A translucent mucus gel covers all studied segments of the gastrointestinal tract during fasting conditions, with the thickest layers in the colon and ileum. Carefully applied suction revealed that the mucus gel was a multi-layered structure comprising a firmly adherent layer covering the mucosa, impossible to remove, and a loosely adherent upper layer. The firmly adherent layer was thick and continuous in the corpus (80μm), antrum (154μm) and colon (116μm), but thin (<20μm) and discontinuous in the small intestine.

    Following mucus removal, a rapid renewal of the loosely adherent layer ensued. The highest rate was observed in the colon with intermediate values in the small intestine. Mucus renewal in the stomach was attenuated on acute luminal application of water extracts from H. pylori (HPE). In animals with a chronic H. pylori infection the mucus renewal rate was unaffected, but the total gastric mucus gel thickness was reduced and the mucus secretory response to luminal acid (pH1) attenuated in the antrum.

    HPE from type I strains acutely reduced corporal mucosal blood flow, measured with laser-Doppler flowmetry, by approximately 15%. The reduction in blood flow was mediated by a heat stable factor other than VacA and CagA. Inhibition of endogenous nitric oxide production with Nω-nitro-l-arginine augmented the decrease. However, ketotifen, a mast cell stabilizer, completely attenuated the effect of the extract as did the platelet activating factor (PAF) receptor-antagonist, WEB2086, thus depicting a detrimental role for the microvascular actions of PAF.

  • 14.
    Atuma, Christer
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Physiology.
    Engstrand, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Physiology.
    Holm, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Physiology.
    Extracts of Helicobacter pylori reduce gastric mucosal blood flow through a VacA- and CagA-independent pathway in rats1998In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 33, no 12, p. 1256-1261Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Helicobacter pylori may interfere with gastroduodenal protective mechanisms. Such effects could be due to a direct interaction with gastric epithelial cells but also to the action of a wide range of secreted and membrane-bound virulence factors. Our aim was to study the acute effects of water extracts produced from H. pylori on gastric mucosal blood flow and acid secretion and to relate them to VacA and CagA activity.

    METHOD: Extracts were produced from strains 88-23 and A5, both wild type; A5VacA, an isogenic mutant lacking expression of the vacuolating cytotoxin (VacA) and the immunodominant antigen (CagA); and Escherichia coli strain ATCC-25922. Bacterial extracts were applied on the exteriorized gastric corporal mucosa in inactin-anaesthetized rats after removal of as much as possible of the mucus layer, during intravital microscopy. Blood flow was measured by means of laser-Doppler flowmetry.

    RESULTS: All H. pylori extracts, including the extract from 88-23 heated to 100 degrees C for 30 min, significantly reduced blood flow by 15%-19%, whereas E. coli had no significant effect on blood flow.

    CONCLUSION: A factor or a combination of factors, other than VacA and CagA released from H. pylori, might compromise the natural defence of the gastric corporal mucosa by reducing mucosal blood flow. The factor is heat-stable and lacking or less potent in E. coli.

  • 15.
    Axelson, Hans W.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Hesselager, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Flink, Roland
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Clinical Neurophysiology.
    Successful localization of the Broca area with short-train pulses instead of "Penfield" stimulation.2009In: Seizure, ISSN 1059-1311, E-ISSN 1532-2688, Vol. 18, no 5, p. 374-375Article in journal (Refereed)
    Abstract [en]

    Direct electrical stimulation of functional cortical areas is a standard procedure in epilepsy and glioma surgery. Many previous studies support that stimulation of the motor cortex with short-train pulses is a less epileptogenic alternative to the 50–60 Hz ‘Penfield’ technique. However, whether the short-train stimulation is useful also in mapping of speech areas is unclear. In this case report we present a patient with oligodendroglioma near the Broca area. Extraoperative electrical stimulation via a subdural grid electrode was primarily performed to locate the speech area. The cortex was stimulated with short-train pulses (5 pulses, 0.5 pulse duration and 3 ms interpulse interval) in addition to 1–3 s 50 Hz stimulation.The patient had speech arrest from both types of stimulation techniques during a naming task. It was however critical that the short (14.5 ms) train stimulation was synchronized with the presentation of the naming objects. If not, there was no speech arrest. Despite this possible pitfall, this case has encouraged us to further try short-train stimulation in attempts to reduce stimulus-triggered seizures during mapping of eloquent areas.

  • 16.
    Babateen, Omar M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Jin, Zhe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Bhandage, Amol K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Korol, Sergiy V.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Westermark, Bengt
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology.
    Nilsson, Karin Forsberg
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology.
    Uhrbom, Lene
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology.
    Smits, Anja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Birnir, Bryndis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    GABA-A receptor currents in a cell line (U3047MG) derived from a human glioblastoma tumor are enhanced by etomidate, propofol and diazepam2014In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 211, no S696, p. 100-100, article id P74Article in journal (Other academic)
  • 17.
    Backman, E. Louis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine.
    Der osmotische Druck bei einigen Wasserkäfern1912In: Pflügers Archiv für die gesamte Physiologie des Menschen und der Tiere, ISSN 0365-267X, Vol. 149, no 1/3, p. 93-114Article in journal (Refereed)
  • 18.
    Backman, E. Louis
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine.
    Sundberg, Carl-Gustaf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine.
    Zur Frage des Verhaltens der Amphibien in verschieden konzentrierten Lösungen: Bemerkungen zu der im ersten und zweiten Hefte von Pflüger's Archiv Bd. 150. 1912 veröffentlichten Mitteilung von Dr. Bruno Brunacci1913In: Pflügers Archiv für die gesamte Physiologie des Menschen und der Tiere, ISSN 0365-267X, Vol. 151, no 1/3, p. 52-56Article in journal (Refereed)
  • 19. Barragan, A.
    et al.
    Weidner, J. M.
    Jin, Zhe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Korpi, E. R.
    Birnir, Bryndis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    GABAergic signalling in the immune system2015In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 213, no 4, p. 819-827Article, review/survey (Refereed)
    Abstract [en]

    The GABAergic system is the main inhibitory neurotransmitter system in the central nervous system (CNS) of vertebrates. Signalling of the transmitter c-aminobutyric acid (GABA) via GABA type A receptor channels or G-protein-coupled type B receptors is implicated in multiple CNS functions. Recent findings have implicated the GABAergic system in immune cell functions, inflammatory conditions and diseases in peripheral tissues. Interestingly, the specific effects may vary between immune cell types, with stage of activation and be altered by infectious agents. GABA/GABA-A receptor-mediated immunomodulatory functions have been unveiled in immune cells, being present in T lymphocytes and regulating the migration of Toxoplasma-infected dendritic cells. The GABAergic system may also play a role in the regulation of brain resident immune cells, the microglial cells. Activation of microglia appears to regulate the function of GABAergic neurotransmission in neighbouring neurones through changes induced by secretion of brain-derived neurotrophic factor. The neurotransmitter-driven immunomodulation is a new but rapidly growing field of science. Herein, we review the present knowledge of the GABA signalling in immune cells of the periphery and the CNS and raise questions for future research.

  • 20.
    Bartlett, Christina S.
    et al.
    Northwestern Univ, Feinberg Cardiovasc Res Inst, Chicago, IL 60611 USA.;Northwestern Univ, Div Nephrol & Hypertens, Chicago, IL 60611 USA..
    Jeansson, Marie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Quaggin, Susan E.
    Northwestern Univ, Feinberg Cardiovasc Res Inst, Chicago, IL 60611 USA.;Northwestern Univ, Div Nephrol & Hypertens, Chicago, IL 60611 USA..
    Vascular Growth Factors and Glomerular Disease2016In: ANNUAL REVIEW OF PHYSIOLOGY, VOL 78, ANNUAL REVIEWS, 2016, p. 437-461Chapter in book (Refereed)
    Abstract [en]

    The glomerulus is a highly specialized microvascular bed that filters blood to form primary urinary filtrate. It contains four cell types: fenestrated endothelial cells, specialized vascular support cells termed podocytes, perivascular mesangial cells, and parietal epithelial cells. Glomerular cell-cell communication is critical for the development and maintenance of the glomerular filtration barrier. VEGF, ANGPT, EGF, SEMA3A, TGF-beta, and CXCL12 signal in paracrine fashions between the podocytes, endothelium, and mesangium associated with the glomerular capillary bed to maintain filtration barrier function. In this review, we summarize the current understanding of these signaling pathways in the development and maintenance of the glomerulus and the progression of disease.

  • 21. Belalov, V. V.
    et al.
    Dyagileva, Yu. O.
    Pavlenko, V. B.
    Kochukhova, Olga M.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.
    Neurophysiological Analysis of Speech Perception in 2.5 to 3.5-Year-Old Orphans and Children Raised in a Family2014In: Neurophysiology (New York), ISSN 0090-2977, E-ISSN 1573-9007, Vol. 46, no 1, p. 79-87Article in journal (Refereed)
    Abstract [en]

    In 2.5-3.5-year-old orphans (n = 41) and children raised in a family (n = 50), we examined specificities of speech perception-related changes in the spectral power density (SPD) of the EEG rhythms. Changes in the SPDs of the theta-, alpha-, beta-, and gamma-rhythms in 16 EEG leads where estimated at presentation of a meaningful speech fragment record (short poem) and of a reversed record of the same signal (direct and reversed speech, respectively). The Bayley Scales of Infant and Toddler Development III demonstrated the existence of noticeable delays in the development of speech in orphans. Comparison of background EEGs and EEGs in the course of listening for direct speech showed that the alpha-rhythm is desynchronized, while the theta-, beta-, and, especially, gamma-oscillations are synchronized upon perception of the above stimulus. In this case, children raised in a family demonstrated significant increases in the gamma-rhythm SPD in 13 leads of both hemispheres; in orphans, this was observed only in 8 loci localized mostly in the left hemisphere. In children of both groups, listening for reversed speech induced mostly desynchronization of all EEG rhythms with the greatest drops in the gamma SPD mostly in the frontal and left temporal leads. Comparison of SPDs of the EEG components (rhythms) at listening for direct and reversed speech demonstrated that powers of theta-, beta-, and gamma-oscillations increased at presentation of a direct (comprehended) speech in children of both groups. In children raised in families, greater SPDs of the gamma-rhythm were observed in 13 leads (differences were most significant in the frontal parts of the left hemisphere). In institutionalized children, the number of leads with significant increments of the gamma-rhythm power was significantly smaller (only 9). It is supposed that smaller increases in the SPD of of gamma-range oscillations in orphans are related to deviations in the processing of a semantic component of speech perception. This can result from insufficient development of cerebral neuronal networks responsible for processing of verbal information.

  • 22.
    Bergfors, Monica
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Improved diagnosis of Carpal tunnel syndrome using amplitude difference between m. Abductor pollicis brevis and m. Pronator quadratus?2008Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The purpose of this study was to investigate the difference in amplitude between M-response from m. Abductor pollicis brevis/m. Pronator quadratus and m. Abductor pollicis brevis/m. Abductor digiti minimi on patients with carpal tunnel syndrome, compared with control subjects. We wanted to see if m. Pronator quadratus is a better alternative than m. Abductor digiti minimi as comparison with m. Abductor pollicis brevis on patients with carpal tunnel syndrome.

    Nerve conduction studies were performed on 20 patients with carpal tunnel syndrome and on 31 healthy subjects.

    The test-retest result shows that this method was reproducible. The amplitude difference of m. Abductor pollicis brevis-m. Abductor digiti minimi, for the patients, was 1,5mV lower and the amplitude for m. Abductor pollicis brevis-m. Pronator quadratus was 2mV lower than for healthy subjects. Two of the patients were outside the 2SD for the m. Abductor pollicis brevis-m. Pronator quadratus difference but not on the m. Abductor pollicis brevis-m. Abductor digiti minimi. This may indicate that m. Pronator quadratus was better than m. Abductor digiti minimi in the comparison with the m. Abductor pollicis brevis amplitude.

  • 23.
    Bergström, Ulrika
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. ekotoxikologi.
    Olsson, Jan
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. ekotoxikologi.
    Hvidsten, Torgeir R
    Komorowski, Jan
    Brandt, Ingvar
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. ekotoxikologi.
    Neurotoxicity of the Olfactory toxicant 2,6-Dichlorophenyl Methylsulphone in Olfactory bulb:Impaired expression of genes relating to neurodegenerative disease2007In: DIOXIN2007, 2007, p. 1841-1844Conference paper (Refereed)
  • 24.
    Bhandage, Amol
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Jin, Zhe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Ólafsson, Einar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Birnir, Bryndis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    The mRNA expression of GABA-A, GABA-B receptor subunits and chloride transporters in peripheral blood mononuclear cells is influenced by gender, pregnancy and depression2015In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 215, p. 91-91Article in journal (Other academic)
  • 25.
    Bhandage, Amol K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Glutamate and GABA signalling components in the human brain and in immune cells2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Glutamate and γ-aminobutyric acid (GABA) are the principal excitatory and inhibitory neurotransmitters in the central nervous system (CNS). They both can activate their ionotropic and metabotropic receptors. Glutamate activates ionotropic glutamate receptors (iGlu - AMPA, kainate and NMDA receptors) and GABA activates GABA-A receptors which are modulated by many types of drugs and substances including alcohol. Using real time quantitative polymerase chain reaction, I have shown that iGlu and/or GABA-A receptor subunits were expressed in the hippocampus dentate gyrus (HDG), orbitofrontal cortex (OFC), dorsolateral prefrontal cortex (DL-PFC), central amygdala (CeA), caudate and putamen of the human brain and their expression was altered by chronic excessive alcohol consumption. It indicates that excitatory and inhibitory neurotransmission may have been altered in the brain of human alcoholics. It is possible that changes in one type of neurotransmitter system may drive changes in another. These brain regions also play a role in brain reward system. Any changes in them may lead to changes in the normal brain functions.

    Apart from the CNS, glutamate and GABA are also present in the blood and can be synthesised by pancreatic islet cells and immune cells. They may act as immunomodulators of circulating immune cells and can affect immune function through glutamate and GABA receptors. I found that T cells from human, rat and mouse lymph nodes expressed the mRNAs and proteins for specific GABA-A receptor subunits. GABA-evoked transient and tonic currents recorded using the patch clamp technique demonstrate the functional GABA-A channel in T cells. Furthermore, the mRNAs for specific iGlu, GABA-A and GABA-B receptor subunits and chloride cotransporters were detected in peripheral blood mononuclear cells (PBMCs) from men, non-pregnant women, healthy and depressed pregnant women. The results indicate that the expression of iGlu, GABA-A and GABA-B receptors is related to gender, pregnancy and mental health and support the notion that glutamate and GABA receptors may modulate immune function. Intra- and interspecies variability exists in the expression and it is further influenced by physiological conditions.

    List of papers
    1. Selective increases of AMPA, NMDA, and kainate receptor subunit mRNAs in the hippocampus and orbitofrontal cortex but not in prefrontal cortex of human alcoholics
    Open this publication in new window or tab >>Selective increases of AMPA, NMDA, and kainate receptor subunit mRNAs in the hippocampus and orbitofrontal cortex but not in prefrontal cortex of human alcoholics
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    2014 (English)In: Frontiers in Cellular Neuroscience, ISSN 1662-5102, E-ISSN 1662-5102, Vol. 8, p. 11-Article in journal (Refereed) Published
    Abstract [en]

    Glutamate is the main excitatory transmitter in the human brain. Drugs that affect the glutamatergic signaling will alter neuronal excitability. Ethanol inhibits glutamate receptors. We examined the expression level of glutamate receptor subunit mRNAs in human post-mortem samples from alcoholics and compared the results to brain samples from control subjects. RNA from hippocampal dentate gyrus (HP-DG), orbitofrontal cortex (OFC), and dorso-lateral prefrontal cortex (DL-PFC) samples from 21 controls and 19 individuals with chronic alcohol dependence were included in the study. Total RNA was assayed using quantitative RT-PCR. Out of the 16 glutamate receptor subunits, mRNAs encoding two AMPA [2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid] receptor subunits GluA2 and GluA3; three kainate receptor subunits GluK2, GluK3 and GluK5 and five NMDA (N-methyl-D-aspartate) receptor subunits GluN1, GluN2A, GluN2C, GluN2D, and GluN3A were significantly increased in the HP-DG region in alcoholics. In the OFC, mRNA encoding the NMDA receptor subunit GluN3A was increased, whereas in the DL-PFC, no differences in mRNA levels were observed. Our laboratory has previously shown that the expression of genes encoding inhibitory GABA-A receptors is altered in the HP-DG and OFC of alcoholics (Jin et al., 2011). Whether the changes in one neurotransmitter system drives changes in the other or if they change independently is currently not known. The results demonstrate that excessive long-term alcohol consumption is associated with altered expression of genes encoding glutamate receptors in a brain region-specific manner. It is an intriguing possibility that genetic predisposition to alcoholism may contribute to these gene expression changes.

    National Category
    Physiology Neurosciences
    Identifiers
    urn:nbn:se:uu:diva-219489 (URN)10.3389/fncel.2014.00011 (DOI)000331053400001 ()24523671 (PubMedID)
    Available from: 2014-03-03 Created: 2014-03-03 Last updated: 2018-01-11Bibliographically approved
    2. Expression of specific ionotropic glutamate and GABA-A receptor subunits is decreased in central amygdala of alcoholics
    Open this publication in new window or tab >>Expression of specific ionotropic glutamate and GABA-A receptor subunits is decreased in central amygdala of alcoholics
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    2014 (English)In: Frontiers in Cellular Neuroscience, ISSN 1662-5102, E-ISSN 1662-5102, Vol. 8, p. 288-Article in journal (Refereed) Published
    Abstract [en]

    The central amygdala (CeA) has a role for mediating fear and anxiety responses. It is also involved in emotional imbalance caused by alcohol abuse and dependence and in regulating relapse to alcohol abuse. Growing evidences suggest that excitatory glutamatergic and inhibitory gamma-aminobutyric acid-ergic (GABAergic) transmissions in the CeA are affected by chronic alcohol exposure. Human post-mortem CeA samples from male alcoholics (n = 9) and matched controls (n = 9) were assayed for the expression level of ionotropic glutamate and GABA-A receptors subunit mRNAs using quantitative real-time reverse transcription-PCB (RT-qPCR). Our data revealed that out of the 16 ionotropic glutamate receptor subunits, mRNAs encoding two AMPA P-amino-3-(3-hydroxy-5-methyl-isoxazol-4-y1)propanoic acid] receptor subunits GluA1 and GluA4; one kainate receptor subunit GluK2; one NMDA (N-methyl-D-aspartate) receptor subunit GluN2D and one delta receptor subunit GluD2 were significantly decreased in the CeA of alcoholics. In contrast, of the 19 GABA-A receptor subunits, only the mRNA encoding the a2 subunit was significantly down-regulated in the CeA of the alcoholics as compared with control subjects. Our findings imply that the down-regulation of specific ionotropic glutamate and GABA-A receptor subunits in the CeA of alcoholics may represent one of the molecular substrates underlying the new balance between excitatory and inhibitory neurotransmission in alcohol dependence.

    National Category
    Neurosciences
    Identifiers
    urn:nbn:se:uu:diva-239603 (URN)10.3389/fncel.2014.00288 (DOI)000344465400002 ()
    Available from: 2014-12-30 Created: 2014-12-29 Last updated: 2018-01-11Bibliographically approved
    3.
    The record could not be found. The reason may be that the record is no longer available or you may have typed in a wrong id in the address field.
    4. Different subtypes of GABA-A receptors are expressed in human, mouse and rat T lymphocytes
    Open this publication in new window or tab >>Different subtypes of GABA-A receptors are expressed in human, mouse and rat T lymphocytes
    2012 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 8, p. e42959-Article in journal (Refereed) Published
    Abstract [en]

    γ-aminobutyric acid (GABA) is the most prominent neuroinhibitory transmitter in the brain, where it activates neuronalGABA-A receptors (GABA-A channels) located at synapses and outside of synapses. The GABA-A receptors are primarytargets of many clinically useful drugs. In recent years, GABA has been shown to act as an immunomodulatory molecule. Wehave examined in human, mouse and rat CD4+ and CD8+ T cells which subunit isoforms of the GABA-A channels areexpressed. The channel physiology and drug specificity is dictated by the GABA-A receptor subtype, which in turn isdetermined by the subunit isoforms that make the channel. There were 5, 8 and 13 different GABA-A subunit isoformsidentified in human, mouse and rat CD4+ and CD8+ T cells, respectively. Importantly, the γ2 subunit that imposesbenzodiazepine sensitivity on the GABA-A receptors, was only detected in the mouse T cells. Immunoblots andimmunocytochemistry showed abundant GABA-A channel proteins in the T cells from all three species. GABA-activatedwhole-cell transient and tonic currents were recorded. The currents were inhibited by picrotoxin, SR95531 and bicuculline,antagonists of GABA-A channels. Clearly, in both humans and rodents T cells, functional GABA-A channels are expressed butthe subtypes vary. It is important to bear in mind the interspecies difference when selecting the appropriate animal modelsto study the physiological role and pharmacological properties of GABA-A channels in CD4+ and CD8+ T cells and whenselecting drugs aimed at modulating the human T cells function.

    National Category
    Neurosciences
    Identifiers
    urn:nbn:se:uu:diva-172532 (URN)10.1371/journal.pone.0042959 (DOI)000307789700016 ()
    Available from: 2012-04-11 Created: 2012-04-11 Last updated: 2018-01-12Bibliographically approved
    5. Expression of GABA receptors subunits in peripheral blood mononuclear cells is gender dependent, altered in pregnancy and modified by mental health
    Open this publication in new window or tab >>Expression of GABA receptors subunits in peripheral blood mononuclear cells is gender dependent, altered in pregnancy and modified by mental health
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    2015 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 213, no 3, p. 575-585Article in journal (Refereed) Published
    Abstract [en]

    AIM: The concept of nerve-driven immunity recognizes a link between the nervous and the immune system. γ-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain and receptors activated by GABA can be expressed by immune cells. Here we examined if the expression of GABA receptors and chloride transporters in human peripheral mononuclear cells (PBMCs) were influenced by gender, pregnancy or mental health.

    METHODS: We used RT-qPCR to determine the mRNA expression level in men (n=16), non-pregnant women (n=19), healthy pregnant women (n=27) and depressed pregnant women (n=15).

    RESULTS: The ρ2 subunit had the most prominent expression level of the GABA-A receptor subunits in all samples. The δ and ρ2 subunits were up-regulated by pregnancy whereas the ε subunit was more frequently expressed in healthy pregnant women than non-pregnant women who, in-turn, commonly expressed the α6 and the γ2 subunits. The β1 and ε subunits expression was altered by depression in pregnant women. The GABA-B1 receptor was up-regulated by depression in pregnant women while the transporters NKCC1 and KCC4 were down-regulated by pregnancy. The changes recorded in the mRNA expression levels imply participation of GABA receptors in establishing and maintaining tolerance in pregnancy. Importantly, the correlation of mental health with the expression of specific receptor subunits reveals a connection between the immune cells and the brain. Biomarkers for mental health may be identified in PBMCs.

    CONCLUSION: The results demonstrate the impact gender, pregnancy and mental health have on expression of GABA receptors plus chloride transporters expressed in human PBMCs.

    National Category
    Physiology
    Identifiers
    urn:nbn:se:uu:diva-240372 (URN)10.1111/apha.12440 (DOI)000348531600007 ()25529063 (PubMedID)
    Available from: 2015-01-07 Created: 2015-01-07 Last updated: 2018-01-11
    6. AMPA, NMDA and kainate glutamate receptor subunits are expressed in human peripheral blood mononuclear cells (PBMCs) where the expression of GluK4 is altered by pregnancy and GluN2D by depression in pregnant women
    Open this publication in new window or tab >>AMPA, NMDA and kainate glutamate receptor subunits are expressed in human peripheral blood mononuclear cells (PBMCs) where the expression of GluK4 is altered by pregnancy and GluN2D by depression in pregnant women
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    2017 (English)In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 305, p. 51-58Article in journal (Refereed) Published
    Abstract [en]

    The amino acid glutamate opens cation permeable ion channels, the iGlu receptors. These ion channels are abundantly expressed in the mammalian brain where glutamate is the main excitatory neurotransmitter. The neurotransmitters and their receptors are being increasingly detected in the cells of immune system. Here we examined the expression of the 18 known subunits of the iGlu receptors families; alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate, N-methyl-D-aspartate (NMDA) and delta in human peripheral blood mononuclear cells (PBMCs). We compared the expression of the subunits between four groups: men, non-pregnant women, healthy pregnant women and depressed pregnant women.

    Out of 18 subunits of the iGlu receptors, mRNAs for 11 subunits were detected in PBMCs from men and nonpregnant women; AMPA: GluA3, GluA4, kainate: GluK2, GluK4, GluK5, NMDA: GluN1, GluN2C, GluN2D, GluN3A, GluN3B, and delta: GluD1. In the healthy and the depressed pregnant women, in addition, the delta GluD2 subunit was identified. The mRNAs for GluK4, GluK5, GluN2C and GluN2D were expressed at a higher level than other subunits. Gender, pregnancy or depression during pregnancy altered the expression of GluA3, GluK4, GluN2D, GluN3B and GluD1 iGlu subunit mRNAs. The greatest changes recorded were the lower GluA3 and GluK4 mRNA levels in pregnant women and the higher GluN2D mRNA level in healthy but not in depressed pregnant women as compared to non-pregnant individuals. Using subunit specific antibodies, the GluK4, GluK5, GluNl, GluN2C and GluN2D subunit proteins were identified in the PBMCs. The results show expression of specific iGlu receptor subunit in the PBMCs and support the idea of physiology-driven changes of iGlu receptors subtypes in the immune cells.

    Keywords
    Glutamate, iGluR subunits, Immune cells, Pregnancy, Depression, Physiology-driven changes
    National Category
    Medical and Health Sciences Neurosciences
    Identifiers
    urn:nbn:se:uu:diva-282410 (URN)10.1016/j.jneuroim.2017.01.013 (DOI)000397694200009 ()28284346 (PubMedID)
    Funder
    Swedish Research Council, 521-2012-1789
    Available from: 2016-04-05 Created: 2016-04-05 Last updated: 2018-01-10Bibliographically approved
  • 26.
    Bhandage, Amol K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Jin, Zhe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Olafsson, Einar B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Sundström-Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Birnir, Bryndis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Expression of GABA receptors subunits in peripheral blood mononuclear cells is gender dependent, altered in pregnancy and modified by mental health2015In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 213, no 3, p. 575-585Article in journal (Refereed)
    Abstract [en]

    AIM: The concept of nerve-driven immunity recognizes a link between the nervous and the immune system. γ-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain and receptors activated by GABA can be expressed by immune cells. Here we examined if the expression of GABA receptors and chloride transporters in human peripheral mononuclear cells (PBMCs) were influenced by gender, pregnancy or mental health.

    METHODS: We used RT-qPCR to determine the mRNA expression level in men (n=16), non-pregnant women (n=19), healthy pregnant women (n=27) and depressed pregnant women (n=15).

    RESULTS: The ρ2 subunit had the most prominent expression level of the GABA-A receptor subunits in all samples. The δ and ρ2 subunits were up-regulated by pregnancy whereas the ε subunit was more frequently expressed in healthy pregnant women than non-pregnant women who, in-turn, commonly expressed the α6 and the γ2 subunits. The β1 and ε subunits expression was altered by depression in pregnant women. The GABA-B1 receptor was up-regulated by depression in pregnant women while the transporters NKCC1 and KCC4 were down-regulated by pregnancy. The changes recorded in the mRNA expression levels imply participation of GABA receptors in establishing and maintaining tolerance in pregnancy. Importantly, the correlation of mental health with the expression of specific receptor subunits reveals a connection between the immune cells and the brain. Biomarkers for mental health may be identified in PBMCs.

    CONCLUSION: The results demonstrate the impact gender, pregnancy and mental health have on expression of GABA receptors plus chloride transporters expressed in human PBMCs.

  • 27.
    Bhandage, Amol K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Hellgren, Charlotte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Jin, Zhe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Olafsson, Einar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Sundström, Iinger Poromaa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Birnir, Bryndis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    GABA-A receptor subunit expression in human peripheral blood mononuclear cells2014In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 211, no S696, p. 86-86, article id P45Article in journal (Other academic)
  • 28.
    Bhandage, Amol K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Jin, Zhe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Bazov, Igor
    Kononenko, Olga
    Bakalkin, Georgy
    Korpi, Esa R
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Birnir, Bryndis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    GABA-A and NMDA receptor subunit mRNA expression is altered in the caudate but not the putamen of the postmortem brains of alcoholics2014In: Frontiers in Cellular Neuroscience, ISSN 1662-5102, E-ISSN 1662-5102, Vol. 8, article id 415Article in journal (Refereed)
    Abstract [en]

    Chronic consumption of alcohol by humans has been shown to lead to impairment of executive and cognitive functions. Here, we have studied the mRNA expression of ion channel receptors for glutamate and GABA in the dorsal striatum of post-mortem brains from alcoholics (n = 29) and normal controls (n = 29), with the focus on the caudate nucleus that is associated with the frontal cortex executive functions and automatic thinking and on the putamen area that is linked to motor cortices and automatic movements. The results obtained by qPCR assay revealed significant changes in the expression of specific excitatory ionotropic glutamate and inhibitory GABA-A receptor subunit genes in the caudate but not the putamen. Thus, in the caudate we found reduced levels of mRNAs encoding the GluN2A glutamate receptor and the δ, ε, and ρ2 GABA-A receptor subunits, and increased levels of the mRNAs encoding GluD1, GluD2, and GABA-A γ1 subunits in the alcoholics as compared to controls. Interestingly in the controls, 11 glutamate and 5 GABA-A receptor genes were more prominently expressed in the caudate than the putamen (fold-increase varied from 1.24 to 2.91). Differences in gene expression patterns between the striatal regions may underlie differences in associated behavioral outputs. Our results suggest an altered balance between caudate-mediated voluntarily controlled and automatic behaviors in alcoholics, including diminished executive control on goal-directed alcohol-seeking behavior.

  • 29.
    Birnir, Bryndis
    et al.
    Molecular and Cellular Physiology, Dept. of Physiological Sciences, Lund University.
    Eghbali, M
    Cox, G B
    Gage, P W
    GABA concentration sets the conductance of delayed GABAA channels in outside-out patches from rat hippocampal neurons.2001In: Journal of Membrane Biology, ISSN 0022-2631, E-ISSN 1432-1424, Vol. 181, no 3, p. 171-83Article in journal (Refereed)
    Abstract [en]

    GABAA channels were activated by GABA in outside-out patches from rat cultured hippocampal neurons. They were blocked by bicuculline and potentiated by diazepam. In 109 of 190 outside-out patches, no channels were active before exposure to GABA (silent patches). The other 81 patches showed spontaneous channel activity. In patches containing spontaneous channel activity, rapid application of GABA rapidly activated channels. In 93 of the silent patches, channels could be activated by GABA but only after a delay that was sometimes as long as 10 minutes. The maximum channel conductance of the channels activated after a delay increased with GABA concentration from less than 10 pS (0.5 microm GABA) to more than 100 pS (10 mm GABA). Fitting the data with a Hill-type equation gave an EC50 value of 33 microm and a Hill coefficient of 0.6. The channels showed outward rectification and were chloride selective. In the presence of 1 microm diazepam, the GABA EC50 decreased to 0.2 microm but the maximum conductance was unchanged. Diazepam decreased the average latency for channel opening. Bicuculline, a GABA antagonist, caused a concentration-dependent decrease in channel conductance. In channels activated with 100 microm GABA the bicuculline IC50 was 19 microm. The effect of GABA on channel conductance shows that the role of the ligand in GABAA receptor channel function is more complex than previously thought.

  • 30.
    Birnir, Bryndis
    et al.
    John Curtin School of Medical Research, Australian National University.
    Eghbali, M
    Everitt, A B
    Gage, P W
    Bicuculline, pentobarbital and diazepam modulate spontaneous GABA(A) channels in rat hippocampal neurons.2000In: British Journal of Pharmacology, ISSN 0007-1188, E-ISSN 1476-5381, Vol. 131, no 4, p. 695-704Article in journal (Refereed)
    Abstract [en]

    Spontaneously opening, chloride-selective channels that showed outward rectification were recorded in ripped-off patches from rat cultured hippocampal neurons and in cell-attached patches from rat hippocampal CA1 pyramidal neurons in slices. In both preparations, channels had multiple conductance states and the most common single-channel conductance varied. In the outside-out patches it ranged from 12 to 70 pS (Vp=40 mV) whereas in the cell-attached patches it ranged from 56 to 85 pS (-Vp=80 mV). Application of GABA to a patch showing spontaneous channel activity evoked a rapid, synchronous activation of channels. During prolonged exposure to either 5 or 100 microM GABA, the open probability of channels decreased. Application of GABA appeared to have no immediate effect on single-channel conductance. Exposure of the patches to 100 microM bicuculline caused a gradual decrease on the single-channel conductance of the spontaneous channels. The time for complete inhibition to take place was slower in the outside-out than in the cell-attached patches. Application of 100 microM pentobarbital or 1 microM diazepam caused 2 - 4 fold increase in the maximum channel conductance of low conductance (<40 pS) spontaneously active channels. The observation of spontaneously opening GABA(A) channels in cell-attached patches on neurons in slices suggests that they may have a role in neurons in vivo and could be an important site of action for some drugs such as benzodiazepines, barbiturates and general anaesthetics.

  • 31.
    Birnir, Bryndis
    et al.
    John Curtin School of Medical Research, Australian National University.
    Everitt, A B
    Gage, P W
    Characteristics of GABAA channels in rat dentate gyrus.1994In: Journal of Membrane Biology, ISSN 0022-2631, E-ISSN 1432-1424, Vol. 142, no 1, p. 93-102Article in journal (Refereed)
    Abstract [en]

    Single channel currents were activated by GABA (0.5 to 5 microM) in cell-attached and inside-out patches from cells in the dentate gyrus of rat hippocampal slices. The currents reversed at the chloride equilibrium potential and were blocked by bicuculline (100 microM). Several different kinds of channel were seen: high conductance and low conductance, rectifying and "nonrectifying." Channels had multiple conductance states. The open probability (Po) of channels was greater at depolarized than at hyperpolarized potentials and the relationship between Po and potential could be fitted with a Boltzmann equation with equivalent valency (z) of 1. The combination of outward rectification and potential-dependent open probability gave very little chloride current at hyperpolarized potentials but steeply increasing current with depolarization, useful properties for a tonic inhibitory mechanism.

  • 32.
    Birnir, Bryndis
    et al.
    John Curtin School of Medical Research, Australian National University.
    Everitt, A B
    Lim, M S
    Gage, P W
    Spontaneously opening GABA(A) channels in CA1 pyramidal neurones of rat hippocampus.2000In: Journal of Membrane Biology, ISSN 0022-2631, E-ISSN 1432-1424, Vol. 174, no 1, p. 21-9Article in journal (Refereed)
    Abstract [en]

    Spontaneous, single channel, chloride currents were recorded in 48% of cell-attached patches on neurones in the CA1 region of rat hippocampal slices. In some patches, there was more than 1 channel active. They showed outward rectification: both channel conductance and open probability were greater at depolarized than at hyperpolarized potentials. Channels activated by gamma-aminobutyric acid (GABA) in silent patches on the same neurones had similar conductance and outward rectification. The spontaneous currents were inhibited by bicuculline and potentiated by diazepam. It was concluded that the spontaneously opening channels were constitutively active, nonsynaptic GABA(A) channels. Such spontaneously opening GABA(A) channels may provide a tonic inhibitory mechanism in these cells and perhaps in other cells that have GABA(A) receptors although not having a GABA(A) synaptic input. They may also be a target for clinically useful drugs such as the benzodiazepines.

  • 33.
    Birnir, Bryndis
    et al.
    Lund University, School of Medicine.
    Korpi, Esa R
    The impact of sub-cellular location and intracellular neuronal proteins on properties of GABA(A) receptors.2007In: Current pharmaceutical design, ISSN 1873-4286, Vol. 13, no 31, p. 3169-77Article in journal (Refereed)
    Abstract [en]

    Most studies of GABA(A) receptor accessory proteins have focused on trafficking, clustering and phosphorylation state of the channel-forming subunits and as a result a number of proteins and mechanisms have been identified that can influence the GABA(A) channel expression and function in the cell plasma membrane. In the light of a growing list of intracellular and transmembrane neuronal proteins shown to affect the fate, function and pharmacology of the GABA(A) receptors in neurons, the concept of what constitutes the native GABA(A) receptor complex may need to be re-examined. It is perhaps more appropriate to consider the associated proteins or some of them to be parts of the receptor channel complex in the capacity of ancillary proteins. Here we highlight some of the effects the intracellular environment has on the GABA-activated channel function and pharmacology. The studies demonstrate the need for co-expression of accessory proteins with the GABA(A) channel-forming subunits in heterologous expression systems in order to obtain the full repertoire of GABA(A) receptors characteristics recorded in the native neuronal environment. Further studies e.g. on gene-modified animal models are needed for most of the accessory proteins to establish their significance in normal physiology and in pathophysiology of neurological and psychiatric diseases. The challenge remains to elucidate the effects that the accessory proteins and processes (e.g. phosphorylation) plus the sub-cellular location have on the "fine-tuning" of the functional and pharmacological properties of the GABA(A) receptor channels.

  • 34.
    Birnir, Bryndis
    et al.
    Department of Physiology, UCLA School of Medicine.
    Lee, H S
    Hediger, M A
    Wright, E M
    Expression and characterization of the intestinal Na+/glucose cotransporter in COS-7 cells.1990In: Biochimica et Biophysica Acta, ISSN 0006-3002, E-ISSN 1878-2434, Vol. 1048, no 1, p. 100-4Article in journal (Refereed)
    Abstract [en]

    Cells derived from the simian kidney, COS-7 cells, were transfected with a eucaryotic expression vector (pEUK-C1) containing the clone for the rabbit intestinal Na+/glucose cotransporter. Expression was monitored after transfection with lipofectin by measuring the initial rate of alpha-methylglucopyranoside (MeGlc) uptake. Cells transfected with vector containing the cDNA for the Na+/glucose cotransporter expressed Na(+)-dependent MeGlc transport. Neither control cells nor cells transfected with vector lacking cloned cDNA expressed the cotransporter. Na(+)-dependent MeGlc uptake into transfected cells was saturable (Km 150 microM), phlorizin-sensitive (Ki 11 microM), and inhibited by sugar analogs (D-glucose greater than MeGlc greater than D-galactose greater than 3-O-methyl-D-glucoside greater than D-allose much greater than L-glucose). Europium was able to mimic Na+ in driving MeGIC uptake. Finally, tunicamycin, an inhibitor of asparagine-linked glycosylation, inhibited the expression of Na(+)-dependent MeGlc transport 80%. We conclude that the rabbit intestinal Na+/glucose cotransporter expressed in COS-7 cell exhibits very similar kinetic properties to that in the native brush border and to that expressed in Xenopus oocytes. In addition, N-linked glycosylation appears to be important for functional expression of this membrane protein.

  • 35.
    Birnir, Bryndis
    et al.
    Department of Physiology, UCLA School of Medicine.
    Loo, D D
    Wright, E M
    Voltage-clamp studies of the Na+/glucose cotransporter cloned from rabbit small intestine.1991In: Pflügers Archiv: European Journal of Physiology, ISSN 0031-6768, E-ISSN 1432-2013, Vol. 418, no 1-2, p. 79-85Article in journal (Refereed)
    Abstract [en]

    Inward Na+ currents associated with the cloned intestinal Na+/glucose cotransporter expressed in Xenopus oocytes have been studied using the two-microelectrode voltage-clamp method. The steady-state current/voltage relations showed voltage-dependent (Vm from +20 to -75 mV) and relatively voltage-independent (Vm from -75 to -150 mV) regions. The apparent Imax for Na+ and glucose increased with negative membrane potentials, and the apparent K0.5 for glucose (K(Glc)0.5) depended on Vm and [Na]o. Increasing [Na]o from 7 to 110 mmol/l had the same effect in decreasing K(Glc)0.5 from 0.44 to 0.03 mmol/l as increasing the Vm from -40 to -150 mV. The I/V curves under saturating conditions (20 mmol/l external sugars and 110 mmol/l [Na]o) were identical for D-glucose, D-galactose, alpha-methyl D-glucopyranoside and 3-O-methyl D-glucoside. The specificity of the cotransporter for sugars was: D-glucose, D-galactose, alpha-methyl D-glucopyranoside greater than 3-O-methyl D-glucoside much greater than D-xylose greater than D-allose much greater than D-mannose. Ki for phlorizin (approximately 10 mumol/l) was independent of Vm at saturating [Na]o. We conclude that a variety of sugars are transported by the cloned Na+/glucose cotransporter at the same maximal rate and that membrane potential affects both the maximal current and the apparent K0.5 of the cotransporter for Na+ and glucose.

  • 36.
    Birnir, Bryndis
    et al.
    John Curtin School of Medical Research, Australian National University.
    Tierney, M L
    Dalziel, J E
    Cox, G B
    Gage, P W
    A structural determinant of desensitization and allosteric regulation by pentobarbitone of the GABAA receptor.1997In: Journal of Membrane Biology, ISSN 0022-2631, E-ISSN 1432-1424, Vol. 155, no 2, p. 157-66Article in journal (Refereed)
    Abstract [en]

    Functional properties of the alpha1beta1 GABAA receptor changes in a subunit-specific manner when a threonine residue in the M2 region at the 12' position was mutated to glutamine. The rate and extent of desensitization increased in all mutants but the rate of activation was faster in the beta1 mutants. A negligible plateau current and abolition of potentiation by pentobarbitone of the GABA-activated current depended on the Thr 12' Gln mutation being present in the beta1 subunit. The Hill coefficient of the peak current response to GABA was reduced to less than one also in a beta1 subunit-specific manner. It was concluded that the beta1 subunit dominated conformational changes activated by GABA.

  • 37.
    Birnir, Bryndis
    et al.
    John Curtin School of Medical Research, Australian National University.
    Tierney, M L
    Howitt, S M
    Cox, G B
    Gage, P W
    A combination of human alpha 1 and beta 1 subunits is required for formation of detectable GABA-activated chloride channels in Sf9 cells.1992In: Proceedings of the Royal Society of London. Biological Sciences, ISSN 0962-8452, E-ISSN 1471-2954, Vol. 250, no 1329, p. 307-12Article in journal (Refereed)
    Abstract [en]

    The baculovirus expression system was used to produce alpha 1 and beta 1 subunits of the human GABAA receptor in Sf9 cells. In cells infected with both alpha 1 and beta 1 recombinant viruses, GABA elicited an outwardly rectifying chloride current that was blocked by bicuculline and potentiated by pentobarbitone. GABA did not produce detectable currents in cells infected with either alpha 1 or beta 1 recombinant viruses alone. In these cells, and in control (non-infected) Sf9 cells, pentobarbitone depressed the leakage current (Ki = 55 microM). Fluorescently labelled monoclonal antibodies to the alpha 1 subunit showed greater amounts of the alpha 1 subunit in cells infected with only the alpha 1 recombinant virus than in cells co-infected with the alpha 1 and beta 1 recombinant viruses. Fluorescence of the plasma membrane was seen in cells co-infected with the alpha 1 and beta 1 recombinant viruses, but was absent in cells infected with only the alpha 1 recombinant virus. It was concluded that the alpha 1 subunit normally interacts with the beta 1 subunit to be transported to the plasma membrane in Sf9 cells.

  • 38.
    Birnir, Bryndis
    et al.
    John Curtin School of Medical Research, Australian National University.
    Tierney, M L
    Lim, M
    Cox, G B
    Gage, P W
    Nature of the 5' residue in the M2 domain affects function of the human alpha 1 beta 1 GABAA receptor.1997In: Synapse, ISSN 0887-4476, E-ISSN 1098-2396, Vol. 26, no 3, p. 324-7Article in journal (Refereed)
    Abstract [en]

    The effects on the functional properties of the alpha 1 beta 1 GABAA receptor when the 5' (alpha 1 Val260; beta 1 Ile255) hydrophobic amino acids in the second transmembrane (M2) region were changed to threonine were examined. In response to a saturating concentration of GABA, the current evoked in mutant receptors showed a decreased rate of desensitization and at equilibrium was a greater fraction of the peak current than in wild-type receptors. The half-saturation concentration of the peak current response to GABA in mutant receptors was comparable to that in wild-type receptors, but the Hill coefficient was reduced to less than one. It was concluded that the 5' amino acids in the M2 region have a role in the conformational changes that occur within the alpha 1 beta 1 GABAA receptor in response to GABA.

  • 39.
    Birnir, Bryndis
    et al.
    John Curtin School of Medical Research, Australian National University.
    Tierney, M L
    Pillai, N P
    Cox, G B
    Gage, P W
    Rapid desensitization of alpha 1 beta 1 GABA A receptors expressed in Sf9 cells under optimized conditions.1995In: Journal of Membrane Biology, ISSN 0022-2631, E-ISSN 1432-1424, Vol. 148, no 2, p. 193-202Article in journal (Refereed)
    Abstract [en]

    alpha 1 and beta 1 subunits of human GABA A receptors were expressed in Sf9 cells using the Sf9-baculovirus system. Better expression was obtained by manipulating the system. Cell growth phase at the time of infection determined the practical range of virus titre, the period postinfection during which cells were useful for signal detection and the maximal current obtained. Cells in the early exponential phase were relatively insensitive to multiplicity of infection (MOI) whereas cells in the mid- to late-exponential phase were highly dependent on MOI and they responded with the largest Cl- current generated by GABA. Channels activated by GABA were chloride-selective. Half the maximum peak whole-cell current was obtained with 11 microM GABA. The time course of Cl- currents activated by saturating GABA concentrations in cells infected with alpha 1 beta 1-recombinant viruses was examined employing a rapid perfusion system which allowed whole-cell solution exchange in less than 1 msec. The current decay could be fitted by 3 to 4 exponentials for the first 8 sec. The initial fast current decrease had a time constant of about 23 msec. No voltage dependence of time constants was detected but the whole-cell IV relation showed outward rectification. Currents were depressed by bicuculline, penicillin and picrotoxin and potentiated by pentobarbitone.

  • 40. Bivol, Liliana Monica
    et al.
    Hultström, Michael
    Gudbrandsen, Oddrun A
    Berge, Rolf K
    Iversen, Bjarne M
    Tetradecylthioacetic acid downregulates cyclooxygenase 2 in the renal cortex of two-kidney, one-clip hypertensive rats.2008In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology, ISSN 0363-6119, E-ISSN 1522-1490, Vol. 295, no 6, p. R1866-73Article in journal (Refereed)
    Abstract [en]

    The effect of tetradecylthioacetic acid (TTA) on the cyclooxygenase (COX) system was investigated in two-kidney, one-clip (2K1C) hypertensive rats. The systolic blood pressure (BP) was increased 6 wk after clipping to 183 +/- 4 vs.127 +/- 3 mmHg in TTA-treated 2K1C rats. The COX1 protein expression was not affected either by the 2K1C procedure or by TTA treatment. COX2 expression was upregulated in both kidneys, but to a greater extent in the clipped kidney. COX2 activity was 16 +/- 3% in control and 38 +/- 2% (P < 0.001) in the clipped kidney, and COX2 protein expression was 1.3 +/- 0.04 in control and 1.6 +/- 0.12 in the clipped kidney (P = 0.006). TTA reduced COX2 activity to control levels. Subcutaneously infusion of a COX2 inhibitor did not reduce BP. Peroxisome proliferator-activated receptors (PPARs) were detected in both kidneys, and PPARdelta was upregulated in the nonclipped kidney after TTA treatment. PGE2 in renal cortex was increased in 2K1C (31 +/- 0.3 in the clipped and 28 +/- 0.2 pg/ml nonclipped kidney, P < 0.001 compared with control). TTA lowered the PGE2 to control levels. Renal blood flow (RBF) response to exogenous ANG II injected in the control and nonclipped kidney was exaggerated after indomethacin treatment but unchanged in the nonclipped kidney of the K1C TTA group. Overall, these results indicate that, after 6 wk of treatment, TTA downregulated the COX2 activity, which have potentially important effects on the regulation of renal hemodynamics but does not explain TTAs ability to lower BP.

  • 41. Bivol, Liliana Monica
    et al.
    Iversen, Bjarne Magnus
    Hultström, Michael
    Department of Clinical Science, University of Bergen, Norway.
    Wallace, Paal W
    Reed, Rolf Kåre
    Wiig, Helge
    Tenstad, Olav
    Unilateral renal ischemia in rats induces a rapid secretion of inflammatory markers to renal lymph and increased peritubular capillary permeability2015In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793Article in journal (Refereed)
    Abstract [en]

    A better understanding of the inflammatory process associated with renal ischemia-reperfusion (IR) injury may be clinically important. In this study we examined the role of the kidney in production of inflammatory mediators by analysing renal lymph after 30 min unilateral occlusion of renal artery followed by 120 min reperfusion, as well as the effect of IR on size selectivity for proteins in both glomerular and peritubular capillaries. All measured mediators increased dramatically in renal hilar lymph, whereas plasma and renal cortical tissue samples returned to control levels after 120 min reperfusion. The responses were differentiated; Interleukin-1β, monocyte chemoattractant protein-1 and leptin were markedly increased in plasma before reperfusion, reflecting an extrarenal response possibly induced by afferent renal nerve activity from the ischemic kidney. Tumour necrosis factor-α  was the only mediator showing elevated lymph to plasma ratio following 30 min reperfusion, indicating that most cytokines were released directly into the bloodstream. The IR induced rise in cytokine levels was paralleled by a significant increase in high molecular weight plasma proteins in both lymph and urine. The latter was shown as a 14-166 fold increase in glomerular sieving coefficient of plasma proteins assessed by a novel proteomic approach, and indicated a temporarily reduced size selectivity of both glomerular and peritubular capillaries. Collectively, our data suggest that cytokines from the ischemic kidney explain most of the rise in plasma concentration, and that the locally produced substances enter the systemic circulation through transport directly to plasma and not via the interstitium to lymph.

  • 42. Bjurstöm, Helen
    et al.
    Wang, JunYang
    Ericsson, Ida
    Bengtsson, Martin
    Liu, Yawei
    Kumar-Mendu, Suresh
    Lund University, Diabetic Centre, CRC, Department of Clinical Sciences.
    Issazadeh-Navikas, Shohreh
    Birnir, Bryndis
    Lund University, Diabetic Centre, CRC, Department of Clinical Sciences.
    GABA, a natural immunomodulator of T lymphocytes2008In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 205, no 1-2, p. 44-50Article in journal (Refereed)
    Abstract [en]

    gamma-aminobutyric acid (GABA) is the main neuroinhibitory transmitter in the brain. Here we show that GABA in the extracellular space may affect the fate of pathogenic T lymphocytes entering the brain. We examined in encephalitogenic T cells if they expressed functional GABA channels that could be activated by the low (nM-1 microM), physiological concentrations of GABA present around neurons in the brain. The cells expressed the alpha1, alpha4, beta2, beta3, gamma1 and delta GABAA channel subunits and formed functional, extrasynaptic-like GABA channels that were activated by 1 microM GABA. 100 nM and higher GABA concentrations decreased T cell proliferation. The results are consistent with GABA being immunomodulatory.

  • 43.
    Borges, Joao Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Bergman, Jakob S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Amato, Marcelo B. P.
    Avenel, Jacques
    Montmerle-Borgdorff, Stephanie
    First-time imaging of effects of inspired oxygen concentration on regional lung volumes and breathing pattern during hypergravity2015In: European Journal of Applied Physiology, ISSN 1439-6319, E-ISSN 1439-6327, Vol. 115, no 2, p. 353-363Article in journal (Refereed)
    Abstract [en]

    Aeroatelectasis can develop in aircrew flying the latest generation high-performance aircraft. Causes alleged are relative hyperoxia, increased gravity in the head-to-foot direction (+G(z)), and compression of legs and stomach by anti-G trousers (AGT). We aimed to assess, in real time, the effects of hyperoxia, +G(z) accelerations and AGT inflation on changes in regional lung volumes and breathing pattern evaluated in an axial plane by electrical impedance tomography (EIT). The protocol mimicked a routine peacetime flight in combat aircraft. Eight subjects wearing AGT were studied in a human centrifuge during 1 h 15 min exposure of +1 to +3.5G(z). They performed this sequence three times, breathing AIR, 44.5 % O-2 or 100 % O-2. Continuous recording of functional EIT enabled uninterrupted assessment of regional lung volumes at the 5th intercostal level. Breathing pattern was also monitored. EIT data showed that +3.5G(z), compared with any moment without hypergravity, caused an abrupt decrease in regional tidal volume (V-T) and regional end-expiratory lung volume (EELV) measured in the EIT slice, independently of inspired oxygen concentration. Breathing AIR or 44.5 % O-2, sub-regional EELV measured in the EIT slice decreased similarly in dorsal and ventral regions, but sub-regional V-T measured in the EIT slice decreased significantly more dorsally than ventrally. Breathing 100 % O-2, EELV and V-T decreased similarly in both regions. Inspired tidal volume increased in hyperoxia, whereas breathing frequency increased in hypergravity and hyperoxia. Our findings suggest that hypergravity and AGT inflation cause airway closure and air trapping in gravity-dependent lung regions, facilitating absorption atelectasis formation, in particular during hyperoxia.

  • 44.
    Borges, João Batista
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Suarez-Sipmann, Fernando
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Bohm, Stephan H
    Tusman, Gerardo
    Melo, Alexandre
    Maripuu, Enn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science.
    Sandström, Mattias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Park, Marcelo
    Costa, Eduardo L V
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Amato, Marcelo
    Regional Lung Perfusion estimated by Electrical Impedance Tomography in a piglet model of lung collapse2011In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 112, no 1, p. 225-236Article in journal (Refereed)
    Abstract [en]

    The assessment of the regional match between alveolar ventilation and perfusion in critically ill patients requires simultaneous measurements of both parameters. Ideally, assessment of lung perfusion should be performed in real-time with an imaging technology which provides, through fast acquisition of sequential images, information about the regional dynamics or regional kinetics of an appropriate tracer. We present a novel electrical impedance tomography (EIT) based method that quantitatively estimates regional lung perfusion based on first-pass kinetics of a bolus of hypertonic saline contrast. Pulmonary blood flow was measured in six piglets during control and unilateral or bilateral lung collapse conditions. The first-pass kinetics method showed good agreement with the estimates obtained by single-photon-emission computerized tomography (SPECT). The mean difference (SPECT minus EIT) between fractional blood flow to lung areas suffering atelectasis was -0.6 %, with a standard deviation of 2.9 %. This method outperformed the estimates of lung perfusion based on impedance-pulsatility. In conclusion, we describe a novel method based on Electrical Impedance Tomography for estimating regional lung perfusion at the bedside. In both, healthy and injured lung conditions, the distribution of pulmonary blood flow as assessed by EIT agreed well with the one obtained by SPECT. The method proposed in this paper has the potential to contribute to a better understanding of the behavior of regional perfusion under different lung and therapeutic conditions.

  • 45. Braun, Matthias
    et al.
    Wendt, Anna
    Birnir, Bryndis
    Department of Physiological Sciences, Lund University.
    Broman, Jonas
    Eliasson, Lena
    Galvanovskis, Juris
    Gromada, Jesper
    Mulder, Hindrik
    Rorsman, Patrik
    Regulated exocytosis of GABA-containing synaptic-like microvesicles in pancreatic beta-cells.2004In: The Journal of General Physiology, ISSN 0022-1295, E-ISSN 1540-7748, Vol. 123, no 3, p. 191-204Article in journal (Refereed)
    Abstract [en]

    We have explored whether gamma-aminobutyric acid (GABA) is released by regulated exocytosis of GABA-containing synaptic-like microvesicles (SLMVs) in insulin-releasing rat pancreatic beta-cells. To this end, beta-cells were engineered to express GABA(A)-receptor Cl(-)-channels at high density using adenoviral infection. Electron microscopy indicated that the average diameter of the SLMVs is 90 nm, that every beta-cell contains approximately 3,500 such vesicles, and that insulin-containing large dense core vesicles exclude GABA. Quantal release of GABA, seen as rapidly activating and deactivating Cl(-)-currents, was observed during membrane depolarizations from -70 mV to voltages beyond -40 mV or when Ca(2+) was dialysed into the cell interior. Depolarization-evoked GABA release was suppressed when Ca(2+) entry was inhibited using Cd(2+). Analysis of the kinetics of GABA release revealed that GABA-containing vesicles can be divided into a readily releasable pool and a reserve pool. Simultaneous measurements of GABA release and cell capacitance indicated that exocytosis of SLMVs contributes approximately 1% of the capacitance signal. Mathematical analysis of the release events suggests that every SLMV contains 0.36 amol of GABA. We conclude that there are two parallel pathways of exocytosis in pancreatic beta-cells and that release of GABA may accordingly be temporally and spatially separated from insulin secretion. This provides a basis for paracrine GABAergic signaling within the islet.

  • 46.
    Broche, Ludovic
    et al.
    Grenoble, France..
    Gaetano, Perchiazzi
    Univ Bari, Bari, Italy..
    Liisa, Porra
    Univ Helsinki, Helsinki, Finland..
    Angela, Tannoia
    Univ Bari, Bari, Italy..
    Mariangela, Pellegrini
    Univ Bari, Bari, Italy..
    Savino, Derosa
    Univ Bari, Bari, Italy..
    Alessandra, Sindaco
    Univ Bari, Bari, Italy..
    Borges, João Batista
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Loic, Degrugilliers
    Univ Picardie Jules Verne, Amiens, France..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Anthony, Wexler
    Univ Calif Davis, Davis, CA 95616 USA..
    Alberto, Bravin
    ESRF, Grenoble, France..
    Sylvia, Verbanck
    Univ Hosp UZ Brussel, Brussels, Belgium..
    Bradford, J. Smith
    Univ Vermont, Burlington, VT USA..
    Jason, H. T. Bates
    Univ Vermont, Burlington, VT USA..
    Sam, Bayat
    Univ Picardie Jules Verne, Amiens, France..
    Dynamic mechanical interactions between neighboring airspaces determine cyclic opening and closure in injured lung2016In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 217, p. 141-141Article in journal (Other academic)
  • 47.
    Brown, Russell
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Neuroscience, Physiology.
    The Influence of the Adenosine A1-receptor on Tubuloglomerular Feedback and Renin Release2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The kidneys play a vital role in the maintenance of extracellular fluid and electrolyte balance and blood pressure. Adenosine, acting through the adenosine A1-receptor (A1R), and nitric oxide have been implicated in several of the regulatory mechanisms in the kidney. The A1R has been found to be present in the renal vasculature, primarily in the afferent arterioles, and in the proximal tubules. The tubuloglomerular feedback mechanism (TGF) is an important regulator of renal vascular tone and glomerular filtration rate. The aim of these investigations was to further elucidate the role of adenosine, acting through the A1R. Investigations on adenosine’s renal effects were performed on transgenic mice lacking the A1R.

    TGF response, elicited by increased distal salt load, was completely abolished in the A1R knockout (A1R -/- ) mice. Basal plasma-renin levels were found to be ~2-fold higher in the A1R -/- compared to the A1R wild-type (A1R+/+) mice. However, salt intake induced inverse changes in plasma-renin levels, indicating that adenosine tonically inhibits macula densa stimulated renin release. Anesthetized and conscious A1R -/- mice, measured telemetrically, had an increased blood pressure, which could be due to the increased plasma-renin levels. Despite the high plasma-renin levels, increased urinary sodium excretion was also observed in the A1R -/- animals. Ischemia caused a decrease in renal function in both A1R+/+ and A1R -/- mice. Ischemic preconditioning protected the A1R+/+ mice from subsequent ischemic episode but had no protective effect on the A1R -/- mice.

    Acute extracellular volume expansion greatly attenuates TGF sensitivity, thus facilitating the elimination of excess fluid. Acute inhibition of nNOS in volume-expanded rats was found to re-establish the attenuated TGF response caused by acute extracellular volume expansion.

    The results show that adenosine, acting through the A1R, plays an important role in mediating TGF response and consequently, regulating renin release, blood pressure, electrolyte balance and other vital renal mechanisms.

    List of papers
    1. Neuronal Nitric Oxide Synthase Inhibition Sensitizes the Tubuloglomerular Feedback Mechanism after Volume Expansion
    Open this publication in new window or tab >>Neuronal Nitric Oxide Synthase Inhibition Sensitizes the Tubuloglomerular Feedback Mechanism after Volume Expansion
    2004 In: Kidney Int, Vol. 65, p. 1349-56Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-91577 (URN)
    Available from: 2004-04-14 Created: 2004-04-14Bibliographically approved
    2. Abolished Tubuloglomerular Feedback and Increased Plasma Renin in Adenosine A1-receptor Deficient Mice
    Open this publication in new window or tab >>Abolished Tubuloglomerular Feedback and Increased Plasma Renin in Adenosine A1-receptor Deficient Mice
    Show others...
    2001 In: Am J Physiol Regulatory Integrative Comp Physiol, no 281, p. R1362-67Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-91578 (URN)
    Available from: 2004-04-14 Created: 2004-04-14Bibliographically approved
    3. The Influence of the Adenosine A1-receptor on Blood Pressure Regulation and Renin Release
    Open this publication in new window or tab >>The Influence of the Adenosine A1-receptor on Blood Pressure Regulation and Renin Release
    Show others...
    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:uu:diva-91579 (URN)
    Available from: 2004-04-14 Created: 2004-04-14 Last updated: 2010-01-13Bibliographically approved
    4. Ischemic Preconditioning does not Protect against Renal Injury in Adenosine A1-receptor Knockout Mice
    Open this publication in new window or tab >>Ischemic Preconditioning does not Protect against Renal Injury in Adenosine A1-receptor Knockout Mice
    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:uu:diva-91580 (URN)
    Available from: 2004-04-14 Created: 2004-04-14 Last updated: 2010-01-13Bibliographically approved
  • 48. Caliandro, P.
    et al.
    Evoli, A.
    Stålberg, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Granata, G.
    Tonali, P.
    Padua, L.
    The difficulty in confirming clinical diagnosis of myasthenia gravis in a seronegative patient: a possible neurophysiological approach2009In: Neuromuscular Disorders, ISSN 0960-8966, E-ISSN 1873-2364, Vol. 19, no 12, p. 825-827Article in journal (Refereed)
    Abstract [en]

    In seronegative myasthenia gravis repetitive nerve stimulation and single-fibre EMG have a crucial diagnostic value but they may be negative, particularly in repetitive nerve stimulation studies. We report the case of a 43-year-old patient with generalized seronegative myasthenia gravis with negative 3Hz repetitive nerve stimulation at Erb’s point and voluntary single-fibre EMG in the orbicularis oculi. We also performed 6 and 12Hz repetitive nerve stimulation at Erb and stimulated single-fibre EMG in the extensor digitorum communis and our findings were pathological. Our data suggest that, for individual patients with an atypical picture characterised by dissociation between a severe clinical pattern and no definite neurophysiological findings on conventional tests, repetitive nerve stimulation with a stimulation rate higher than 3Hz and/or stimulated single-fibre EMG with an increasing stimulation rate may be helpful.

  • 49.
    Carlbom, Charlotte
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Measurement of ejection fraction of the left ventricular - A comparison between echocardiography and isotope angiography2008Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 50.
    Castensson, Anja
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolutionary Biology, Evolutionary Biology.
    Emilsson, Lina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Sundberg, Rolf
    Jazin, Elena
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Evolutionary Biology.
    Decrease of serotonin receptor 2C in schizophrenia brains identified by high-resolution mRNA expression analysis2003In: Biological Psychiatry, ISSN 0006-3223, E-ISSN 1873-2402, Vol. 54, no 11, p. 1212-1221Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: RNA expression profiling can provide hints for the selection of candidate susceptibility genes, for formulation of hypotheses about the development of a disease, and/or for selection of candidate gene targets for novel drug development. We measured messenger RNA expression levels of 16 candidate genes in brain samples from 55 schizophrenia patients and 55 controls. This is the largest sample so far used to identify genes differentially expressed in schizophrenia brains. METHODS: We used a sensitive real-time polymerase chain reaction methodology and a novel statistical approach, including the development of a linear model of analysis of covariance type. RESULTS: We found two genes differentially expressed: monoamine oxidase B was significantly increased in schizophrenia brain (p =.001), whereas one of the serotonin receptor genes, serotonin receptor 2C, was significantly decreased (p =.001). Other genes, previously proposed to be differentially expressed in schizophrenia brain, were invariant in our analysis. CONCLUSIONS:The differential expression of serotonin receptor 2C is particularly relevant for the development of new atypical antipsychotic drugs. The strategy presented here is useful to evaluate hypothesizes for the development of the disease proposed by other investigators.

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