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  • 51.
    Tejle, Katarina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Medicinsk mikrobiologi. Linköpings universitet, Hälsouniversitetet.
    Leishmania donovani Lipophosphoglycan: Modulation of Macrophage and Dendritic Cell Function2006Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Leishmania donovani is a blood-borne tropicial parasite, which infects humans through bites by Phlebotomus sandflies. The parasite survives and multiplies inside macrophages in inner organs, and causes the deadly disease visceral leishmaniasis (Kala-Azar).

    Macrophages and dendritic cells (DC) are professional antigen-presenting cells involved in the initiation of immune responses. Immature DC are present in all tissues where they internalise and process antigen, in response to which they migrate from tissue, into draining lymphoid organs, undergo maturation and present antigens to lymphocytes. Control measures for leishmaniasis include testing of new diagnostics and development of affordable and effective vaccines for humans.

    Lipophosphoglycan (LPG) is the major surface component of Leishmania donovani promastigotes. LPG comprises a membrane-anchoring lysophosphatidylinositol part and an extracellular chain of disaccharide phosphates. These repetitions are crucial for parasite survival inside macrophages following phagocytosis. LPG has several specific effects on the host cell including inhibition of protein kinase C (PKC) activity, and inhibition of phagosomal maturation, a process requiring depolymerization of periphagosomal F-actin.

    Confocal microscopy and image analysis were used to follow F-actin dynamics in single macrophages during phagocytosis of L. donovani promastigotes and LPG-coated particles. F-actin did not depolymerize, but instead progressively polymerized around phagosomes with LPG-containing prey. This correlated with reduced translocation of PKCα to the phagosome and blocked phagosomal maturation. LPG also inhibited cortical actin turnover, which could be the underlying cause of the reduced uptake of LPG-containing prey. Extracellular- and intracellular calcium was necessary for phagocytosis, periphagosomal F-actin breakdown and phagosomal maturation in macrophages interacting with unopsonized prey,and for the action of LPG.

    We also studied F-actin turnover in macrophages overexpressing dominant-negative (DN) PKCα. DN PKCα macrophages showed increased amounts of cortical F-actin, decreased phagocytic capacity, inhibition of periphagosomal F-actin breakdown and defective phagosomal maturation. When DN PKCα macrophages interacted with LPG-containing prey, phagocytosis was almost completely blocked.

    Moreover, we found that Leishmania promastigotes and particularly LPG inhibit DC maturation and detachment from distinct surfaces. Thus, LPG from Leishmania donovani could directly inhibit DC migration to lymphoid organs, antigen-presentation and development of immunity.

    Delarbeid
    1. Leishmania donovani lipophosphoglycan causes periphagosomal actin accumulation: correlation with impaired translocation of PKCα and defective phagosome maturation
    Åpne denne publikasjonen i ny fane eller vindu >>Leishmania donovani lipophosphoglycan causes periphagosomal actin accumulation: correlation with impaired translocation of PKCα and defective phagosome maturation
    Vise andre…
    2001 (engelsk)Inngår i: Cellular Microbiology, ISSN 1462-5814, E-ISSN 1462-5822, Vol. 3, nr 7, s. 439-447Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Lipophosphoglycan (LPG) is the major surface glycoconjugate of Leishmania donovani promastigotes. The repeating disaccharide–phosphate units of LPG are crucial for promastigote survival inside macrophages and establishment of infection. LPG has a number of effects on the host cell, including inhibition of PKC activity, inhibition of nitric oxide production and altered expression of cytokines. LPG also inhibits phagosomal maturation, a process requiring depolymerization of periphagosomal F-actin. In the present study, we have characterized the dynamics of F-actin during the phagocytosis of L. donovani promastigotes in J774 macrophages. We observed that F-actin accumulated progressively around phagosomes containing wild-type L. donovani promastigotes during the first hour of phagocytosis. Using LPG-defective mutants and yeast particles coated with purified LPG, we obtained evidence that this effect could be attributed to the repeating units of LPG. LPG also disturbed cortical actin turnover during phagocytosis. The LPG-dependent accumulation of periphagosomal F-actin correlated with an impaired recruitment of the lysosomal marker LAMP1 and PKCα to the phagosome. Accumulation of periphagosomal F-actin during phagocytosis of L. donovani promastigotes may contribute to the inhibition of phagosomal maturation by physically preventing vesicular trafficking to and from the phagosome.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-13848 (URN)10.1046/j.1462-5822.2001.00127.x (DOI)
    Tilgjengelig fra: 2006-05-23 Laget: 2006-05-23 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    2. Phagocytosis and phagosome maturation are regulated by calcium in J774 macrophages interacting with un-opsonized prey
    Åpne denne publikasjonen i ny fane eller vindu >>Phagocytosis and phagosome maturation are regulated by calcium in J774 macrophages interacting with un-opsonized prey
    2002 (engelsk)Inngår i: Bioscience Reports, ISSN 0144-8463, Vol. 22, nr 5-6, s. 529-540Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Phagocytosis by neutrophils, macrophages, and other professional phagocytes requires rapid remodeling of actin. Early phagosomes are surrounded by a rim of F-actin that is disassembled during phagosomoal maturation. Breakdown of periphagosomal F-actin and phagolysosome fusion are calcium dependent processes in neutrophils interacting with serum-opsonized prey, but appears to be calcium independent in macrophages interacting with serum- or IgG-opsonized prey. In the present study, we found that calcium was necessary for phagocytosis, breakdown of periphagosomal F-actin, and phagosomal maturation in J774 macrophages interacting with unopsonized prey. We also observed that lipophosphoglycan (LPG) from Leishmania donovani promastigotes required calcium to exert its inhibitory effect on macrophage phagocytosis and periphagosomal F-actin breakdown. We conclude that calcium is essential for phagocytosis, depolymerization of periphagosomal F-actin, and phagosomal maturation in J774 macrophages interacting with unopsonized prey, as well as for proper functioning of LPG.

    Emneord
    Macrophage, phagocytosis, calcium, actin, phagosome maturation, lipophosphoglycan
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-13849 (URN)10.1023/A:1022025903688 (DOI)
    Tilgjengelig fra: 2006-05-23 Laget: 2006-05-23 Sist oppdatert: 2013-09-18
    3. Role of protein kinase C α for uptake of unopsonized prey and phagosomal maturation in macrophages
    Åpne denne publikasjonen i ny fane eller vindu >>Role of protein kinase C α for uptake of unopsonized prey and phagosomal maturation in macrophages
    Vise andre…
    2003 (engelsk)Inngår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 302, nr 4, s. 653-658Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Protein kinase C α (PKCα) participates in F-actin remodeling during phagocytosis and phagosomal maturation in macrophages. Leishmania donovani promastigotes, which inhibit phagosomal maturation, cause accumulation of periphagosomal F-actin instead of the dissassembly observed around other prey [Cell. Microbiol. 7 (2001) 439]. This accumulation is induced by promastigote lipophosphoglycan (LPG), which has several effects on macrophages including inhibition of PKCα. To investigate a possible connection between PKCα and LPG’s effects on actin dynamics, we utilized RAW264.7 macrophages overexpressing dominant-negative PKCα (DN PKCα). We found increased cortical F-actin and decreased phagocytic capacity, as well as defective periphagosomal F-actin breakdown and inhibited phagosomal maturation in the DN PKCα-overexpressing cells, effects similar to those seen in controls subjected to LPG-coated prey. The results indicate that PKCα is involved in F-actin turnover in macrophages and that PKCα-dependent breakdown of periphagosomal F-actin is required for phagosomal maturation, and endorse the hypothesis that intracellular survival of L. donovani involves inhibition of PKCα by LPG.

    Emneord
    PKCα, Actin, Phagocytosis, Macrophage, Lipophosphoglycan
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-13850 (URN)10.1016/S0006-291X(03)00231-6 (DOI)
    Tilgjengelig fra: 2006-05-23 Laget: 2006-05-23 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    4. Leishmania donovani promastigotes block maturation, increase integrin expression and inhibit detachment of human monocytederived dendritic cells – a role for lipophosphoglycan (LPG)
    Åpne denne publikasjonen i ny fane eller vindu >>Leishmania donovani promastigotes block maturation, increase integrin expression and inhibit detachment of human monocytederived dendritic cells – a role for lipophosphoglycan (LPG)
    Manuskript (Annet vitenskapelig)
    Identifikatorer
    urn:nbn:se:liu:diva-13851 (URN)
    Tilgjengelig fra: 2006-05-23 Laget: 2006-05-23 Sist oppdatert: 2010-01-13
  • 52.
    Thorfinn, Johan
    Linköpings universitet, Institutionen för biomedicin och kirurgi. Linköpings universitet, Hälsouniversitetet.
    Studies on sitting pressure and buttock microcirculation: aiming at developing an alarm in the prevention of pressure ulcers in patients with spinal cord injuries2006Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Pressure ulcers in patients with spinal cord injuries are a major problem, the prevalence in this group being reported as high as 20 – 30 percent. Most pressure ulcers develop around the pelvic girdle, and the key-contributing factor in the development of pressure ulcers is ischaemia due to longstanding pressure. Loss of mobility and lack of sensation below the level of injury are prominent risk factors for the development of pressure ulcers. Although many factors are known to contribute to pressure ulcer development, the exact aetiology is not completely clear. Prevention is suggested as the best way to deal with the problem. The studies in this thesis investigate some aspects of the physiology of sitting in patients with spinal cord injuries and healthy controls, aiming at developing a pressure ulcer alarm device to aid in the prevention of pressure ulcers. Methods used are laser Doppler perfusion imaging (LDPI) for measurement of superficial skin blood flow, as well microdialysis and a microelectrode (Licox®) to measure direct and indirect signs of ischaemia. In addition sitting pressures are mapped. The main findings are that patients with spinal cord injuries have almost four-fold mean maximum sitting pressures 43 and 49 N/cm2, left and right buttock) compared with healthy controls 12 and 13 N/cm2, left and right buttock). In the subcutaneous fat in healthy individuals, the tissue oxygen pressure decreases significantly during 30 minutes of sitting on a wheel chair cushion 13,7 mmHg) compared with 30 minutes of sitting on a hard surface 19,8 mmHg) implying that the tissues deep in the skin are exposed to a reduction in blood supply. This is also confirmed by a decrease in extracellular glucose during sitting for 30 minutes on a hard surface 1,8 mmol/L) and on a wheel chair cushion 1,7 mmol/L). The post-sitting reactive hyperaemia is dependent on duration of sitting in both patients and healthy subjects. It seems to be attenuated in patients in the sitting position but intensified while lying prone. Furthermore, four repeated loadings on a hard surface 15 minutes of sitting followed by five minutes of rest) without allowing the tissues to return to resting perfusion results in a significantly increasing reactive hyperaemia for each loading in healthy subjects, suggesting that it is important to unload the buttock skin completely before the next sitting period starts. This thesis also describes the construction of an alarm device that measures surface interface pressures during sitting continuously in eight predefined points, to alert the user by an audible signal after a given period of time when the pressure has reached a dangerously high level. It is concluded that the reactive hyperaemia that is observed in the buttock skin after sitting, as well as the reduction in glucose and oxygen in adipose tissue during sitting, are due to a reduction in blood supply relative or absolute ischaemia) caused by a compression of the vasculature by the ischial tuberosities. These findings imply a multilayer aetiology in pressure ulcer development. The altered hyperaemic reaction in patients with spinal cord injuries after sitting is possibly related to alterations in sympathetic activity due to the cord lesion. Lastly, the alarm device is supposed to be an aid to pressure ulcer prevention in patients with spinal cord injuries who lack normal sensory feedback.

    Delarbeid
    1. Sitting pressure and perfusion of buttock skin in paraplegic and tetraplegic patients, and in healthy subjects: a comparative study
    Åpne denne publikasjonen i ny fane eller vindu >>Sitting pressure and perfusion of buttock skin in paraplegic and tetraplegic patients, and in healthy subjects: a comparative study
    2002 (engelsk)Inngår i: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery, ISSN 2000-656X, E-ISSN 2000-6764, Vol. 36, nr 5, s. 279-283Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The distribution of sitting pressure and ability to respond with reactive hyperaemia were studied in a group of paraplegic and tetraplegic patients (n = 8) with spinal cord lesions and healthy controls (n = 10) using a pressure sensitive plate and laser Doppler perfusion imager. The results show that the mean sitting pressure of the patients was 9.9 N/cm2 (left) and 11.7 N/cm2 (right) compared with 3.5 N/cm2 (left) and 3.6 N/cm2 (right) in controls. The differences were significant on both the left (p < 0.01) and right (p < 0.05) sides. The maximum pressure in patients was 42.9 N/cm2 (left) and 48.7 N/cm2 (right), and in controls 12.0 N/cm2 (left) and 12.9 (right) (p < 0.01). Both groups showed a reduction in skin perfusion in the seat area during sitting compared with unloaded resting, and in the controls it was significantly increased (p < 0.001 on both sides) during the reactive hyperaemic phase immediately after sitting. Compared with the preload values, the patients showed a similar but slightly weaker picture significant on the right side (p < 0.05), but not on the left. The hyperaemia was not uniformly distributed, but occurred where the pressure was greater than 2 N/cm2. There was no correlation between the amount of reactive hyperaemia and absolute values of sitting pressures. We conclude that tetraplegic and paraplegic patients have significantly higher sitting pressures than normal controls, and that the hyperaemic response in the buttock region in the upright position after pressure load is slightly weaker in the patients, which could be of importance for the development of decubitus ulcers.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-25222 (URN)10.1080/028443102320791824 (DOI)9661 (Lokal ID)9661 (Arkivnummer)9661 (OAI)
    Tilgjengelig fra: 2009-10-07 Laget: 2009-10-07 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    2. Perfusion of the skin of the buttocks in paraplegic and tetraplegic patients, and in healthy subjects after a short and long load
    Åpne denne publikasjonen i ny fane eller vindu >>Perfusion of the skin of the buttocks in paraplegic and tetraplegic patients, and in healthy subjects after a short and long load
    2006 (engelsk)Inngår i: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery, ISSN 2000-656X, E-ISSN 2000-6764, Vol. 40, nr 3, s. 153-160Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    In patients with spinal cord injuries (n=8) and healthy controls (n=8) the hyperaemic response in the buttock skin after sitting on a hard surface was studied using a laser Doppler perfusion imager. They sat for three minutes (short load), or 15 minutes (long load). An exponential mathematical function was used to compare the mean perfusion during the observed interval. The results showed that preloading perfusion is significantly higher among patients than healthy subjects. In both groups, the microcirculation of the skin increased significantly after loading, and peak perfusion was significantly lower after the short load. The mean perfusion was higher among the patients after both loadings, which suggests that there was stronger ischaemic provocation. The main outcome was that there was a dose-response relation between duration of loading and intensity of reactive hyperaemia, and that patients with spinal cord injuries have greater perfusion before and after loading than healthy controls.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-37630 (URN)10.1080/02844310600693179 (DOI)36825 (Lokal ID)36825 (Arkivnummer)36825 (OAI)
    Tilgjengelig fra: 2009-10-10 Laget: 2009-10-10 Sist oppdatert: 2018-03-26bibliografisk kontrollert
    3. Perfusion of buttock skin in healthy volunteers after long and short repetitive loading evaluated by laser Doppler perfusion imager
    Åpne denne publikasjonen i ny fane eller vindu >>Perfusion of buttock skin in healthy volunteers after long and short repetitive loading evaluated by laser Doppler perfusion imager
    2007 (engelsk)Inngår i: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery, ISSN 2000-656X, E-ISSN 2000-6764, Vol. 41, nr 6, s. 297-302Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Frequent unloading is vital to avoid pressure ulcers of the seat area in patients with injuries to the spinal cord. The duration of unloading is probably as important as that of the sitting period in the prophylaxis of pressure ulcers. The aim of this study was to investigate the microcirculatory reactions after occlusion of the buttock skin after repeated ischaemic provocation. The perfusion of buttock skin was studied with a laser Doppler perfusion imager (LDPI) in healthy people after short and long periods of sitting (repeated four times). The perfusion increased significantly during the consecutive loadings compared with the first loading, and this effect was more profound after the long load. Repeated periods of ischaemia of the buttock skin without allowing the tissues to recover resulted in increasing reactive hyperaemia, and are therefore probably more damaging than single loadings. This is important when establishing clinical guidelines for the prophylaxis of pressure ulcers in patients with spinal cord injuries.

    Emneord
    Decubitus ulcer, Laser Doppler perfusion imaging, Reactive hyperaemia, Repetitive loading, Sitting pressure, Spinal cord injury
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-47789 (URN)10.1080/02844310701633249 (DOI)
    Tilgjengelig fra: 2009-10-11 Laget: 2009-10-11 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    4. Sitting can cause ischaemia in the subcutaneous tissue of the buttocks, which implicates multilayer tissue damage in the development of pressure ulcers
    Åpne denne publikasjonen i ny fane eller vindu >>Sitting can cause ischaemia in the subcutaneous tissue of the buttocks, which implicates multilayer tissue damage in the development of pressure ulcers
    2009 (engelsk)Inngår i: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery, ISSN 2000-656X, E-ISSN 2000-6764, Vol. 43, nr 2, s. 82-89Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    A better understanding of how pressure ulcers develop in the buttocks will improve prophylactic measures. Our aim was to investigate signs of reduced perfusion and ischaemia in the subcutaneous fat in the buttocks during sitting. A microelectrode was used to quantify oxygen (pO2). Metabolites that indicate aerobic or anaerobic metabolism (glucose, lactate, pyruvate, and glycerol) were quantified using microdialysis. Sixteen healthy people were studied while they sat on a wheel chair cushion, and a hard surface. Sitting pressures were mapped, and the thickness of the subcutaneous fatty layer was measured. The results showed that pO2 and glucose were significantly reduced during sitting, and for pO2 the effect is significantly more profound during sitting on a hard surface. After loading, both glucose and pO2 increased significantly. We conclude that the subcutaneous adipose tissue covering the ischial tuberosities becomes ischaemic during sitting. This finding supports the theory that not only is the skin involved in early development of pressure ulcers, but also the deeper tissues.

    Emneord
    Pressure ulcer development, spinal cord injury, ischaemia, reperfusion, microdialysis, microelectrode, adipose tissue, sitting pressure
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-17697 (URN)10.1080/02844310902749455 (DOI)
    Tilgjengelig fra: 2009-04-16 Laget: 2009-04-14 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    5. A pressure-controlled alarm and monitoring device for pressure ulcer prophylaxis in patients with traumatic spinal cord injury: a prototype
    Åpne denne publikasjonen i ny fane eller vindu >>A pressure-controlled alarm and monitoring device for pressure ulcer prophylaxis in patients with traumatic spinal cord injury: a prototype
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Patients with spinal cord injury are prone to develop pressure ulcers, especially around the pelvic girdle and in the buttocks. Treatment of pressure ulcer is demanding for the health care system in terms of personal and economic resources, and for the patient because of extensive conservative or surgical treatments to achieve healing. The prevention of pressure ulcers is therefore of major importance for this patient group. A contributing factor to the development of pressure ulcers is the lack of biosensory feedback below the level of injury, that results in a lack of impulses to the patient to change body position. In this paper we describe the construction of a technical device that monitors sitting pressures in a wheel chair cushion, and alerts the user when the pressure has reached a critical level for a period of time long enough to risk tissue damage. This device also saves pressure data continuously for retrospective analysis to evaluate the patients' sitting and unloading behaviour, and to study the effect of pressure relieving wheel chair cushions over longer periods of time.

    Emneord
    Pressure ulcer prevention, alarm device, sitting pressure, spinal cord injury, prototype
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-84827 (URN)10.1007/978-3-642-03885-3_184 (DOI)
    Tilgjengelig fra: 2012-10-23 Laget: 2012-10-23 Sist oppdatert: 2014-08-29bibliografisk kontrollert
  • 53.
    Toss, Henrik
    et al.
    Linköpings universitet, Institutionen för teknik och naturvetenskap, Fysik och elektroteknik. Linköpings universitet, Tekniska fakulteten.
    Lönnqvist, Susanna
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Nilsson, David
    Acreo Swedish ICT AB, Norrköping, Sweden.
    Sawatdee, Anurak
    Acreo Swedish ICT AB, Norrköping, Sweden.
    Nissa, Josefin
    Linköpings universitet, Institutionen för teknik och naturvetenskap, Fysik och elektroteknik. Linköpings universitet, Tekniska fakulteten.
    Fabiano, Simone
    Linköpings universitet, Institutionen för teknik och naturvetenskap, Fysik och elektroteknik. Linköpings universitet, Tekniska fakulteten.
    Berggren, Magnus
    Linköpings universitet, Institutionen för teknik och naturvetenskap, Fysik och elektroteknik. Linköpings universitet, Tekniska fakulteten.
    Kratz, Gunnar
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Sinnescentrum, Hand- och plastikkirurgiska kliniken US.
    Simon, Daniel T
    Linköpings universitet, Institutionen för teknik och naturvetenskap, Fysik och elektroteknik. Linköpings universitet, Tekniska fakulteten.
    Ferroelectric Surfaces for Cell Release2017Inngår i: Synthetic metals, ISSN 0379-6779, E-ISSN 1879-3290, Vol. 228, s. 99-104Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Adherent cells cultured in vitro must usually, at some point, be detached from the culture substrate. Presently, the most common method of achieving detachment is through enzymatic treatment which breaks the adhesion points of the cells to the surface. This comes with the drawback of deteriorating the function and viability of the cells. Other methods that have previously been proposed include detachment of the cell substrate itself, which risks contaminating the cell sample, and changing the surface energy of the substrate through thermal changes, which yields low spatial resolution and risks damaging the cells if they are sensitive to temperature changes. Here cell culture substrates, based on thin films of the ferroelectric polyvinylidene fluoride trifluoroethylene (PVDF-TrFE) co-polymer, are developed for electroactive control of cell adhesion and enzyme-free detachment of cells. Fibroblasts cultured on the substrates are detached through changing the direction of polarization of the ferroelectric substrate. The method does not affect subsequent adhesion and viability of reseeded cells.

  • 54.
    Van Vliet, Jolanda S
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    Rasanen, Leena
    Department of Food and Environmental Sciences, Division of Nutrition, University of Helsinki, Finland..
    Gustafsson, Per A
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Barn- och ungdomspsykiatri. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Barn- och ungdomspsykiatriska kliniken.
    Nelson, Nina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Barn- och ungdomskliniken i Linköping.
    Overweight perception among adolescent girls in relation to appearance of female characteristics2014Inngår i: Paediatrics and Health, ISSN 2052-935X, Vol. 2, nr 1, s. 1-7Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Overweight perception has been shown to be important for health related adolescent behavior, particularly in girls. Body perception may be affected by bodily changes, especially changes visible for others. Female pubertal development is characterized by many physical changes, such as accelerated growth and altered body fat distribution. This study examined the role of appearance of female characteristics in the risk for overweight perception among healthy adolescent girls.

    Methods: 220 girls, aged 11–16, provided self-reports on body perception and pubertal maturation before anthropometric measurements of height, weight, hip and waist circumference (WC). Logistic regression modeling was used to study the appearance of pubertal characteristics in relation to body perception.

    Results: Of the 76 girls (35%) perceiving themselves as overweight, only 14 and 36 girls were overweight according to body mass index and waist circumference respectively. Girls reporting breast development and acne (n=144) were more likely to perceive themselves as overweight than girls who did not report this appearance (n=76). These findings persist after adjusting for overweight according to WC. Non-overweight (n=170) rather than overweight girls reporting characteristics (n=50) were at risk of perceiving themselves overweight.

    Conclusions: Girls may confuse natural changes occurring during adolescent development with being overweight. It is therefore important to improve the understanding about the physical changes that normally occur during puberty along with the girls' own perception of these bodily changes among girls themselves, their parents, at schools, and other healthcare services.

  • 55.
    Vicente Carrillo, Alejandro
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Sperm Membrane Channels, Receptors and Kinematics: Using boar spermatozoa for drug toxicity screening2016Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Internal fertilization usually implies that a spermatozoon, with intact attributes for zygote formation, passes all hurdles during its transport through the female genitalia and reaches the oocyte. During this journey, millions to billions of other spermatozoa perish. Spermatozoa are highly differentiated motile cells without synthetic capabilities. They generate energy via glycolysis and oxidative phosphorylation to sustain motility and to maintain the stability and functionality of their plasma membrane. In vivo, they spend their short lifespan bathing in female genital tract fluids of different origins, or are in vitro exposed to defined media during diverse sperm handling i.e. extension, cryopreservation, in vitro fertilization, etc. Being excitable cells, spermatozoa respond in vivo to various stimuli during pre-fertilization (capacitation, hyperactivation, oocyte location) and fertilization (acrosome reaction, interaction with the oocyte) events, mediated via diverse membrane ion-conducting channels and ligand-gated receptors. The present Thesis has mapped the presence and reactivity (sperm intactness and kinematics) of selected receptors, water and ion channels in ejaculated boar spermatozoa. The final aim was to find a relevant alternative cell type for in vitro bioassays that could ease the early scrutiny of candidate drugs as well as decreasing our needs for experimental animals according to the 3R principles. Spermatozoa are often extended, cooled and thawed to warrant their availability as fertile gametes for breeding or in vitro testing. Such manipulations stress the cells via osmotic variations and hence spermatozoa need to maintain membrane intactness by controlling the exchange of water and the common cryoprotectant glycerol, via aquaporins (AQPs). Both AQPs-7 and -9 were studied for membrane domain changes in cauda- and ejaculated spermatozoa (un-processed, extended, chilled or frozen-thawed). While AQP-9 maintained location through source and handling, thawing of ejaculated spermatozoa clearly relocated the labelling of AQP-7, thus appearing as a relevant marker for non-empirical studies of sperm cryopreservation. Alongside water, spermatozoa interact with calcium (Ca2+) via the main Ca2+ sperm channel CatSper. Increments in intracellular Ca2+ initiate motility hyperactivation and the acrosome reaction. The four subunits of the CatSper channel were present in boar spermatozoa, mediating changes in sperm motility under in vitro capacitation-inducing conditions (increased extracellular Ca2+ availability and bicarbonate) or challenge by the CatSper antagonists mibefradil and NNC 55-0396. Uterine and oviduct fluids are richest in endogenous opioids as β-endorphins during mating and ovulation. Both μ- and δ- opioid receptors were present in boar spermatozoa modulating sperm motility, as in vitro challenge with known agonists (μ: morphine; δ: DPDPE and κ: U 50488) and antagonists (μ: naloxone; δ: naltrindole and κ: nor-binaltrorphimine) showed that the μ-opioid receptor maintained or increased motility while the δ-opioid receptor mediated decreased motility over time. Finally, boar spermatozoa depicted dose-response effects on sperm kinematics and mitochondrial potential following in vitro challenge with 130 pharmacological drugs and toxic compounds as well as with eight known mito-toxic compounds. In conclusion, boar spermatozoa expressing functional water (AQPs-7 and -9) and ion (CatSper 1-4) channels as well as μ- and δ-opioid receptors are able to adapt to stressful environmental variations, capacitation and pharmacological compounds and drug components. Ejaculated sperm suspensions are easily and painlessly obtained from breeding boars, and are suitable biosensors for in vitro drug-induced testing, complying with the 3R principles of reduction and replacement of experimental animals, during early toxicology screening.

    Delarbeid
    1. Membrane Stress During Thawing Elicits Redistribution of Aquaporin 7 But Not of Aquaporin 9 in Boar Spermatozoa
    Åpne denne publikasjonen i ny fane eller vindu >>Membrane Stress During Thawing Elicits Redistribution of Aquaporin 7 But Not of Aquaporin 9 in Boar Spermatozoa
    2016 (engelsk)Inngår i: Reproduction in domestic animals, ISSN 0936-6768, E-ISSN 1439-0531, Vol. 51, nr 5, s. 665-679Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Freezing of boar spermatozoa includes the cryoprotectant glycerol, but renders low cryosurvival, owing to major changes in osmolarity during freezing/thawing. We hypothesize that aquaporins (AQPs) 7 and 9 adapt their membrane domain location to these osmotic challenges, thus maintaining sperm homeostasis. Western blotting (WB) and immunocytochemistry (ICC) at light and electron microscope levels with several commercial primary antibodies and protocols explored AQP location on cauda epididymal and ejaculated spermatozoa (from different fractions of the ejaculate), unprocessed, extended, chilled and frozen-thawed. Although differences in WB and ICC labelling were seen among antibodies, AQP-7 was conspicuously located in the entire tail and cytoplasmic droplet in caudal spermatozoa, being restricted to the mid-piece and principal piece domains in ejaculated spermatozoa. AQP-9 was mainly localized in the sperm head in both caudal and ejaculated spermatozoa. While unaffected by chilling (+5°C), freezing and thawing of ejaculated spermatozoa clearly relocated the head labelling of AQP-7, but not that of AQP-9. In vitro mimicking of cell membrane expansion during quick thawing maintained the localization of AQP-9 but relocated AQP-7 towards the acrosome. AQP-7, but not AQP-9, appears as a relevant marker for non-empirical studies of sperm handling.

    sted, utgiver, år, opplag, sider
    Blackwell Verlag, 2016
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-130228 (URN)10.1111/rda.12728 (DOI)000388334100005 ()27405395 (PubMedID)
    Merknad

    Funding agencies: Swedish Research Council VR, Stockholm [521-2011-6553]; Research Council FORMAS, Stockholm [221-2011-512]; FORSS (Forskningsradet i Sydostra Sverige), Sweden [473121]

    Tilgjengelig fra: 2016-07-19 Laget: 2016-07-19 Sist oppdatert: 2018-03-23bibliografisk kontrollert
    2. The CatSper channel modulates boar sperm motility during capacitation.
    Åpne denne publikasjonen i ny fane eller vindu >>The CatSper channel modulates boar sperm motility during capacitation.
    2017 (engelsk)Inngår i: Reproductive biology, ISSN 2300-732X, Vol. 17, nr 1, s. 69-78Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The cation channel of sperm (CatSper) comprises four transmembrane subunits specifically expressed in human, equine, murine and ovine spermatozoa, apparently implicated in capacitation, hyperactivation and acrosome exocytosis. Western blotting and immunocytochemistry showed hereby that CatSper subunits are also present in boar spermatozoa, primarily over the sperm neck, tail and cytoplasmic droplets; albeit CatSper -1 presented in addition some distribution over the membrane of the acrosome and CatSper -2 and -4 over the membrane of the post-acrosome. The role of the Catsper channel in boar spermatozoa was investigated by extending the spermatozoa in media containing different calcium (Ca(2+)) availability and exposure to the capacitation-trigger bicarbonate, to progesterone or CatSper inhibitors (Mibefradil and NNC 55-0396), separately or sequentially, at physiological and toxicological doses. Extracellular Ca(2+) availability, combined with bicarbonate exposure (capacitation-inducing conditions) decreased sperm motility, similarly to when spermatozoa incubated in capacitation-inducing conditions was exposed to Mibefradil and NNC 55-0396. Exposure of these spermatozoa to progesterone did not cause significant changes in sperm motility and nor did it revert its decrease induced by CatSper antagonists. In conclusion, the CatSper channel regulates sperm motility during porcine capacitation-related events in vitro.

    sted, utgiver, år, opplag, sider
    Elsevier, 2017
    Emneord
    CatSper, Spermatozoa, Capacitation, Sperm motility, Boar
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-134398 (URN)10.1016/j.repbio.2017.01.001 (DOI)000397370900009 ()28077244 (PubMedID)2-s2.0-85009212156 (Scopus ID)
    Merknad

    Funding agencies: The Swedish Research council VR, Stockholm [521-2011-6553]; Research Council FORMAS, Stockholm [221-2011-512]; FORSS (Forskningsradet i Sydostra Sverige, Sweden [473121]

    Tilgjengelig fra: 2017-02-23 Laget: 2017-02-23 Sist oppdatert: 2017-05-29bibliografisk kontrollert
    3. The mu (µ) and delta (δ) opioid receptors modulate boar sperm motility
    Åpne denne publikasjonen i ny fane eller vindu >>The mu (µ) and delta (δ) opioid receptors modulate boar sperm motility
    2016 (engelsk)Inngår i: Molecular Reproduction and Development, ISSN 1040-452X, E-ISSN 1098-2795, Vol. 83, nr 8, s. 724-734Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Endogenous and exogenous opioids modulate reproductive functions in target cells via opioid receptors (µ, δ, and κ). Sperm motility is a metric of gamete functionality, and serves as a suitable parameter for in vitro drug-induced toxicity assays. This study identifies the presence and location of opioid receptors in pig spermatozoa as well as their functional response after in vitro challenge with known agonists (morphine [µ]; [D-Pen 2,5]-enkephanile [δ]; and U 50488 [κ]) and antagonists (naloxone [µ]; naltrindole [δ]; and nor-binaltrorphimine [κ]). Only the µ- and δ-opioid receptors were present in the sperm plasma membrane, overlying the acrosome, neck, and principal piece. Challenge experiments with agonists and antagonists identified both µ- and δ-opioid receptors as regulators of sperm kinematics, wherein µ maintains or increases sperm movement whereas δ decreases sperm motility over time. This article is protected by copyright. All rights reserved.

    sted, utgiver, år, opplag, sider
    John Wiley & Sons, 2016
    Emneord
    opioids, membrane receptors, kinematics, pig
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-130181 (URN)10.1002/mrd.22675 (DOI)000387014800007 ()27391529 (PubMedID)
    Merknad

    Funding agencies: Swedish Research Council VR, Stockholm [521-2011-6553]; Research Council FORMAS, Sweden [221-2011-512]; Research Council in Southeast Sweden (FORSS), Sweden [378091/31297]

    Tilgjengelig fra: 2016-07-14 Laget: 2016-07-14 Sist oppdatert: 2017-11-28bibliografisk kontrollert
    4. Boar spermatozoa successfully predict mitochondrial modes of toxicity: Implications for drug toxicity testing and the 3R principles
    Åpne denne publikasjonen i ny fane eller vindu >>Boar spermatozoa successfully predict mitochondrial modes of toxicity: Implications for drug toxicity testing and the 3R principles
    Vise andre…
    2015 (engelsk)Inngår i: Toxicology in Vitro, ISSN 0887-2333, E-ISSN 1879-3177, Vol. 29, nr 3, s. 582-591Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Replacement of animal testing by in vitro methods (3-R principles) requires validation of suitable cell models, preferably obtained non-invasively, defying traditional use of explants. Ejaculated spermatozoa are highly dependent on mitochondrial production and consumption of ATP for their metabolism, including motility display, thus becoming a suitable model for capturing multiple modes of action of drugs and other chemicals acting via mitochondrial disturbance. In this study, a hypothesis was tested that the boar spermatozoon is a suitable cell type for toxicity assessment, providing a protocol for 3R-replacement of animals for research and drug-testing. Boar sperm kinetics was challenged with a wide variety of known frank mito-toxic chemicals with previously shown mitochondrial effects, using a semi-automated motility analyser allied with real-time fluorescent probing of mitochondrial potential (MitoTracker and JC-1). Output of this sperm assay (obtained after 30 min) was compared to cell viability (ATP-content, data obtained after 24-48 h) of a hepatome-cell line (HepG2). Results of compound effects significantly correlated (P less than 0.01) for all sperm variables and for most variables in (HepG2). Dose-dependent decreases of relative ATP content in HepG2 cells correlated to sperm speed (r= 0.559) and proportions of motile (r = 0.55) or progressively motile (r = 0.53) spermatozoa. The significance of the study relies on the objectivity of computerized testing of sperm motility inhibition which is comparable albeit of faster output than somatic cell culture models. Sperm suspensions, easily and painlessly obtained from breeding boars, are confirmed as suitable biosensors for preclinical toxicology screening and ranking of lead compounds in the drug development processes.

    sted, utgiver, år, opplag, sider
    Elsevier, 2015
    Emneord
    Sperm; Motility; Mitochondria; Drug; Toxicity; Boar
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-117655 (URN)10.1016/j.tiv.2015.01.004 (DOI)000352050100019 ()25624015 (PubMedID)
    Merknad

    Funding Agencies|Swedish Research Council (VR); Research Council Formas, Stockholm, Sweden

    Tilgjengelig fra: 2015-05-12 Laget: 2015-05-06 Sist oppdatert: 2017-12-04
  • 56.
    Vánky, Farkas
    Linköpings universitet, Institutionen för medicin och hälsa, Thoraxkirurgi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Hjärtcentrum, Thorax-kärlkliniken.
    Surgery for aortic stenosis: with special reference to myocardial metabolism, postoperative heart failure and long-term outcome2006Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Postoperative heart failure (PHF) remains a major determinant of the outcome after cardiac surgery. However, characteristics of and risk factors for PHF after valve surgery have received little attention.

    Post-ischaemic disturbances of myocardial metabolism that may contribute to PHF and are amenable to metabolic treatment have been identified early after coronary surgery (CABG). Knowledge derived from these studies may not be applicable to other patient groups. We therefore studied myocardial energy metabolism in 20 elective patients undergoing aortic valve replacement (AVR) for isolated aortic stenosis (AS). The metabolic studies indicated that myocardial oxidative metabolism had not fully recovered when the procedure was completed. Free fatty acids were the only major substrates taken up by the heart. Signs of preoperative and postoperative metabolic adaptation with substantial uptake of glutamate, previously demonstrated in patients with coronary artery disease, were found. Postoperative infusion of glutamate, (2 mL/kg body weight and hour of 0.125 M solution) based on assessment of myocardial glutamate requirements in CABG patients, resulted in a two-fold increase in myocardial glutamate uptake and a seven-fold increase in AV differences across the leg. This was associated with a significant myocardial uptake of lactate and metabolic changes in the leg suggesting mitigation of net amino acid loss and peripheral tissue lipolysis.

    Characteristics of and risk factors for PHF were evaluated in 398 patients undergoing isolated AVR for AS from 1 January 1995 to 31 December 2000. These were compared with 398 patients, matched for age and sex, undergoing on-pump isolated CABG. Forty-five AVR and 47 CABG patients fulfilled criteria for PHF and these were studied in detail. PHF usually presented at weaning from cardiopulmonary bypass. After CABG it was closely associated with preoperative ischaemic events and intraoperatively acquired myocardial infarction. Potential causes and eliciting events of PHF after AVR for AS were obvious only in one-third of the patients. Risk factors for PHF after AVR for AS indicated either pre-existing myocardial dysfunction, increased right or left ventricular after-load, or intraoperatively acquired myocardial injury. PHF was associated with high early mortality after CABG, whereas the consequences of PHF after AVR for AS became evident only with time, resulting in a 42% five-year mortality. Although PHF had a different temporal impact on late mortality after CABG and AVR for AS, it emerged as the statistically most significant risk factor for mortality occurring within 5 years from surgery both after AVR for AS and after CABG. Potential implications of our findings include needs for greater focus on preoperative surveillance of patients with AS for optimal timing of surgery, mitigation of intraoperatively acquired myocardial injury and tailoring of treatment for PHF. Furthermore, the findings have implications for long-term follow up of AS patients after surgery.

    Delarbeid
    1. Different characteristics of postoperative heart failure after surgery for aortic stenosis and coronary disease
    Åpne denne publikasjonen i ny fane eller vindu >>Different characteristics of postoperative heart failure after surgery for aortic stenosis and coronary disease
    2004 (engelsk)Inngår i: Scandinavian Cardiovascular Journal, ISSN 1401-7431, Vol. 38, nr 3, s. 152-158Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Objective: Postoperative heart failure (PHF) remains a major determinant of outcome after cardiac surgery. However, possible differences in characteristics of PHF after valve surgery and coronary surgery (CABG) have received little attention. Therefore, this issue was studied in patients undergoing aortic valve replacement (AVR) and CABG, respectively.

    Design: Three hundred and ninety-eight patients undergoing isolated AVR for aortic stenosis were compared with 398 patients, matched for age and sex, undergoing on-pump isolated CABG. Forty-five AVR and 47 CABG patients required treatment for PHF and these were studied in detail.

    Results: The AVR group had longer aortic cross-clamp time and higher rate of isolated right ventricular heart failure postoperatively. Myocardial ischemia during induction and perioperative myocardial infarction were more common in the CABG group. One-year mortality was 8.9% in the AVR group vs 25.5% in the CABG group (p = 0.05).

    Conclusions: The incidence of PHF was similar in both groups but different characteristics were found. Isolated right ventricular failure and PHF precipitated by septicemia were more common in AVR patients. PHF was more clearly associated with myocardial ischemia and infarction in CABG patients, which could explain their less favorable survival.

    Emneord
    aortic valve surgery, complications of surgery, coronary artery bypass surgery, heart failure, prognosis
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-14018 (URN)10.1080/14017430410029734 (DOI)
    Tilgjengelig fra: 2006-09-28 Laget: 2006-09-28 Sist oppdatert: 2009-08-21
    2. Risk factors for postoperative heart failure in patients operated on for aortic stenosis
    Åpne denne publikasjonen i ny fane eller vindu >>Risk factors for postoperative heart failure in patients operated on for aortic stenosis
    2006 (engelsk)Inngår i: The Annals of Thoracic Surgery, ISSN 0003-4975, Vol. 81, nr 4, s. 1297-1304Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background

    Risk factors for postoperative heart failure (PHF) have not been specifically studied in valve surgery although it has been acknowledged that patient variables may have a more profound influence on postoperative outcome than valve-related factors.

    Methods

    All patients undergoing isolated aortic valve replacement for aortic stenosis from January 1995 to December 2000 in the southeast region of Sweden were studied (n = 398). Forty-five patients with aortic valve replacement required treatment for PHF. Univariate and multivariate logistic regression analysis was carried out to identify risk factors for PHF.

    Results

    Thirty-day mortality was 6.7% versus 1.4% for patients with and without PHF, respectively (p = 0.05). With regard to clinical presentation of aortic stenosis, angina was associated with reduced risk, whereas history of congestive heart failure increased the risk for PHF. Five preoperative (hypertension, history of congestive heart failure, severe systolic left ventricular dysfunction, pulmonary hypertension, preoperative hemodynamic instability) and two intraoperative (aortic cross-clamp time, intraoperative myocardial infarction) variables were identified as independent risk factors for PHF. Patient–prosthesis mismatch did not influence the risk of PHF significantly.

    Conclusions

    Postoperative heart failure was associated with a marked increase in postoperative mortality and morbidity. Risk factors for PHF were variables indicating preexisting myocardial dysfunction, increased right or left ventricular afterload, and intraoperative myocardial injury. Our results highlight issues concerning cross-clamp time and myocardial protection, particularly for patients with preoperatively compromised myocardial function. Asymptomatic patients with significant aortic stenosis should be considered for surgery before substantial echocardiographic evidence of left ventricular dysfunction or increased pulmonary artery pressure develops.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-14019 (URN)10.1016/j.athoracsur.2005.11.036 (DOI)
    Tilgjengelig fra: 2006-09-28 Laget: 2006-09-28 Sist oppdatert: 2009-06-08
    3. Influence of early postoperative heart failure on five-year survival after surgery for aortic stenosis compared with CABG
    Åpne denne publikasjonen i ny fane eller vindu >>Influence of early postoperative heart failure on five-year survival after surgery for aortic stenosis compared with CABG
    Manuskript (Annet vitenskapelig)
    Identifikatorer
    urn:nbn:se:liu:diva-14020 (URN)
    Tilgjengelig fra: 2006-09-28 Laget: 2006-09-28 Sist oppdatert: 2010-01-13
    4. Myocardial metabolism before and after valve replacement for aortic stenosis
    Åpne denne publikasjonen i ny fane eller vindu >>Myocardial metabolism before and after valve replacement for aortic stenosis
    Vise andre…
    2006 (engelsk)Inngår i: Journal of Cardiovascular Surgery, ISSN 0021-9509, E-ISSN 1827-191X, Vol. 47, nr 3, s. 305-313Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    AIM: Post ischemic disturbances of myocardial metabolism that may contribute to postoperative heart failure and are accessible to metabolic treatment have been identified early after coronary surgery. Knowledge derived from these studies may not be applicable to other patient groups. Therefore we studied myocardial energy metabolism in patients operated for isolated aortic stenosis.

    METHODS: Twenty patients undergoing isolated aortic valve replacement (AVR) because of aortic stenosis without significant regurgitation were studied before and immediately after surgery. Myocardial uptake of oxygen and energy substrates was assessed with coronary sinus catheter technique.

    RESULTS: Free fatty acids (FFA) were the main source of myocardial energy before and after AVR. A significant uptake of lactate was only recorded preoperatively. A significant uptake of glutamate of the same magnitude as previously described in coronary patients was found pre- and postoperatively. Postoperatively a relative decrease of myocardial oxygen extraction ratio (P<0.001) and oxygen consumption (P=0.14) by approximately 20% was observed.

    CONCLUSION: Preoperative and postoperative metabolic adaptation with substantial uptake of glutamate, previously claimed to be due to chronic or repetitive ischemia, was demonstrated. The results indicate that oxidative metabolism had not fully recovered when the procedure was completed. However, the potentially unfavorable postoperative metabolic state with predominant reliance on FFA as energy source was out-balanced by the unloading effect of AVR with a reduction in myocardial oxygen extraction.

    Emneord
    Aged, Amino Acids, Aortic Valve Stenosis, Biological Markers, Blood Glucose, Energy Metabolism, Fatty Acids, Female, Glycerol, Heart Valve Prosthesis Implantation, Hemodynamics, Humans, Lactic Acid, Male, Middle Aged, Myocardium, Oxygen, Oxygen Consumption, Postoperative Care, Preoperative Care, Treatment Outcome
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-14021 (URN)
    Tilgjengelig fra: 2006-09-28 Laget: 2006-09-28 Sist oppdatert: 2017-12-13
    5. Does glutamate influence myocardial and peripheral tissue metabolism after aortic valve replacement for aortic stenosis?
    Åpne denne publikasjonen i ny fane eller vindu >>Does glutamate influence myocardial and peripheral tissue metabolism after aortic valve replacement for aortic stenosis?
    2006 (engelsk)Inngår i: Clinical Nutrition, ISSN 0261-5614, E-ISSN 1532-1983, Vol. 25, nr 6, s. 913-922Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background & aims

    Glutamate plays an important role for myocardial metabolism in association with ischaemia. Patients with coronary artery disease characteristically demonstrate increased uptake of glutamate. Improved recovery of myocardial metabolism and haemodynamic state after coronary surgery has been reported in patients treated with glutamate infusion. However, the effect of glutamate has not been studied after other cardiac surgical procedures. In addition, the effects of glutamate on peripheral tissue metabolism remain to be described.

    Methods

    Twenty patients undergoing surgery for aortic stenosis were studied after randomisation to blinded infusion of glutamate or saline during 1 h immediately after skin closure. Myocardial and leg tissue metabolism were assessed with organ balance techniques.

    Results

    Postoperative glutamate infusion induced a marked increase in myocardial and leg tissue uptake of glutamate. This was associated with a significant uptake of lactate in the heart. The negative arterial–venous differences of amino acids and free fatty acids across the leg were significantly smaller in the glutamate group. Haemodynamic state remained stable and did not differ between groups.

    Conclusion

    The heart and peripheral tissues consumed the exogenously administered glutamate after surgery for aortic stenosis. Potentially favourable effects of glutamate on myocardial and peripheral tissue metabolism are suggested.

    Emneord
    Glutamate; Myocardial metabolism; Humans; Aortic stenosis; Surgery
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-14022 (URN)10.1016/j.clnu.2006.04.002 (DOI)
    Tilgjengelig fra: 2006-09-28 Laget: 2006-09-28 Sist oppdatert: 2017-12-13
    6. Assessment of myocardial glutamate requirements early after coronary artery bypass surgery
    Åpne denne publikasjonen i ny fane eller vindu >>Assessment of myocardial glutamate requirements early after coronary artery bypass surgery
    Vise andre…
    1998 (engelsk)Inngår i: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 32, nr 3, s. 145-152Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Glutamate is an important substrate for the intermediary metabolism of the heart, particularly in association with ischemia. Early after coronary artery bypass surgery (CABG) myocardial uptake of glutamate seems to be limited by substrate availability (arterial levels). However, glutamate is not an innocuous substrate. As arterial levels of glutamate are important both for myocardial uptake and adverse effects, an attempt was made to determine a minimum dose of glutamate sufficient to supply the needs of the heart after CABG. Ten patients received and infusion of 220-240 ml of 0.1 M L-glutamic acid solution at varying rates during two 30-min periods, starting 2 h after uncomplicated elective CABG. Intravenous glutamate infusion caused a dose-dependent linear increase in arterial glutamate and an increased myocardial uptake of glutamate. However, myocardial uptake of glutamate correlated with arterial levels only at lower infusion rates. Although maximal peak uptake in individual patients (6.6 ± 1.1 μmol/min) occurred at an average increase of arterial whole blood glutamate of 172 ± 34 μmol/L, the greatest impact on myocardial glutamate uptake was achieved by increasing arterial whole blood glutamate by less than 100 μmol/L. This implies that an infusion rate of 30-40 mg glutamate/kg BW/h could suffice to achieve a maximal or near maximal myocardial glutamate uptake in most patients after CABG. The adequacy of this dosage remains to be confirmed in high-risk patients.

    Emneord
    adverse effects, biological transport, cardiac surgery, coronary artery disease, dose-response, human glutamate, metabolism, myocardium
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-14023 (URN)10.1080/14017439850140102 (DOI)
    Tilgjengelig fra: 2006-09-28 Laget: 2006-09-28 Sist oppdatert: 2017-12-13bibliografisk kontrollert
  • 57.
    Wanby, Pär W.
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet.
    On certain genetic and metabolic risk factors for carotid stenosis and stroke2006Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The present study evaluated genetic and metabolic factors influencing the risk of acute cerebrovascular disease (CVD) and internal carotid artery stenosis (ICA stenosis) in a Swedish community. The threonine (T) containing protein of the FABP2 A54T gene polymorphism has a greater affinity for long chain fatty acids (FFAs) than the alanine (A) containing protein. This altered affinity for FFAs has been shown to affect the intestinal absorption of fatty acids and consequently the fatty acid composition of serum lipids, in particularly postprandially. Endothelium derived NO is a potent vasodilator and antiatherogenic agent. Asymmetric dimethyl arginine (ADMA) is an endogenous competitive inhibitor of endothelial nitric oxide synthase (eNOS). ADMA has been shown to be involved in the pathogenesis of atherosclerotic disease, and ADMA inhibits eNOS by displacement of L-arginine from the enzyme, which in turn is believed to affect the amount of NO available within the endothelium.

    The FABP2 A54T gene polymorphism was analyzed in 407 patients with acute CVD and also in a subset of these patients whose carotids had been evaluated with ultrasound. Both the FABP2 polymorphism and a common polymorphism of the eNOS gene, Glu298Asp, were analyzed in a different population consisting of 54 matched pairs of patients with ICA stenosis and controls. ADMA levels were measured in both study populations.

    We found that the T54 allele was more frequent in patients with transient ischaemic attacks (TIA), and that the TT genotype was more prevalent in young, non-smoking patients with CVD than in controls.

    Increased concentrations of ADMA were observed in cardio-embolic infarction and TIA, but not significantly in non-cardio-embolic infarction nor in haemorrhagic stroke. In multivariate logistic regression models, CVD increased across quartiles of ADMA in all subgroups, but this association was only significant in the TIA group. A decreased arginine/ADMA ratio, a measure of NO availability was associated with CVD in the entire study population. Patients with severe carotid stenosis had significantly higher ADMA levels than the controls. Allele and genotype frequencies of the FABP2 and eNOS polymorphisms did not differ between patients with ICA stenosis and controls.

    Our results indicate that ADMA is a strong marker for TIA and severe ICA stenosis, and that relative defiency of arginine, measured as L-arginine/ADMA, is present in acute CVD.

    We also conclude that a common polymorphism of the FABP2 gene increases susceptibility to ischaemic stroke and TIA.

    Delarbeid
    1. The FABP2 gene polymorphism in cerebrovascular disease
    Åpne denne publikasjonen i ny fane eller vindu >>The FABP2 gene polymorphism in cerebrovascular disease
    Vise andre…
    2004 (engelsk)Inngår i: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 110, nr 6, s. 355-360Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Objective – Earlier studies have shown that the fatty acid binding protein 2 (FABP2) T54 allele is associated with dyslipidemia, which in turn correlates with the incidence of cerebrovascular disease (CVD). To assess whether the FABP2 gene A54T polymorphism is associated with an increased risk of CVD we undertook a case–control study.

    Materials and methods – A total of 407 patients diagnosed with acute CVD and 158 control subjects were genotyped for the A54T polymorphism using a PCR-RFLP method.

    Results – Allele and genotype frequencies of the FABP2 A54T polymorphism did not differ between subjects with acute CVD (TT, 9.6%; TA, 41.0%; AA, 49.4%) and controls (TT, 7.6%; TA, 41.1%; AA, 51.3%; P = ns) or in the following subgroups of CVD compared with controls: non-cardioembolic infarction (n = 252), intracerebral hemorrhage (n = 23), and cardioembolic infarction (n = 91). In transient ischemic attacks (TIAs) (n = 41) the combined TT and TA genotype frequency (TT + TA, 65.9%) was more frequent than in controls (48.7%) (P = 0.05). Furthermore, the TT genotype was more frequent in non-smoking patients under the age of 70 (n = 77) with a non-cardioembolic infarction (TT, 18.2%) compared with controls (7.6%) (P = 0.024).

    Conclusions – Our findings suggest an involvement of the FABP2 (A54T) gene polymorphism in the pathogenesis of CVD. The FABP2 T54 allele appears to be a genetic susceptibility marker for TIA and non-cardioembolic infarction at younger onset.

    sted, utgiver, år, opplag, sider
    Wiley-Blackwell, 2004
    Emneord
    FABP2, polymorphism, stroke, genetics
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-14007 (URN)10.1111/j.1600-0404.2004.00335.x (DOI)
    Tilgjengelig fra: 2006-09-28 Laget: 2006-09-28 Sist oppdatert: 2018-05-25
    2. Genetic variation of the intestinal fatty acid-binding protein 2 gene in carotid atherosclerosis
    Åpne denne publikasjonen i ny fane eller vindu >>Genetic variation of the intestinal fatty acid-binding protein 2 gene in carotid atherosclerosis
    2005 (engelsk)Inngår i: Vascular Medicine, ISSN 1358-863X, Vol. 10, nr 2, s. 103-108Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The alanine (A) to threonine (T) substitution at codon 54 of the intestinal fatty acid-binding protein 2 (FABP2) has been associated with dyslipidaemia and other characteristics of the metabolic syndrome, which in turn is a risk factor for cerebrovascular disease. The aim of this study was to investigate whether the A54T polymorphism in the FABP2 gene is associated with internal carotid artery (ICA) stenosis in stroke patients. Swedish subjects initially diagnosed with acute cerebrovascular disease (n = 196) that had been assessed with ultrasound of the carotid arteries were identified and grouped depending on whether a stenosis was found. The subjects were genotyped for the A54T polymorphism using a PCR-RFLP method. In a multivariate logistic-regression analysis, where known risk factors for atherosclerosis were fixed (diabetes, systolic blood pressure, age and smoking), having the FABP2 T allele was a significant risk factor for ICA stenosis (odds ratio 2.9; 95% confidence interval, 1.1-7.7; p = 0.04) together with diabetes (odds ratio 4.9; 95% confidence interval, 1.8-14; p < 0.01). Age, smoking and blood pressure did not reach statistical significance. In conclusion, our result supports the hypothesis that the FABP2 A54T polymorphism is associated with ICA stenosis.

    Emneord
    carotid atherosclerosis, FABP2, genetics, polymorphism
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-14008 (URN)10.1191/1358863x05vm609oa (DOI)
    Tilgjengelig fra: 2006-09-28 Laget: 2006-09-28 Sist oppdatert: 2010-08-20
    3. Asymmetric dimethylarginine (ADMA) as a risk marker for stroke and TIA in a Swedish population
    Åpne denne publikasjonen i ny fane eller vindu >>Asymmetric dimethylarginine (ADMA) as a risk marker for stroke and TIA in a Swedish population
    Vise andre…
    2006 (engelsk)Inngår i: Atherosclerosis, ISSN 0021-9150, Vol. 185, nr 2, s. 271-277Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, has been shown to be involved in the pathogenesis of atherosclerosis. The present study was initiated to investigate the role of ADMA as a risk marker of acute cerebrovascular disease (CVD).

    We examined 363 CVD patients and 48 controls. The ADMA concentration (mean ± S.D., μmol/L) in controls was 0.50 ± 0.06. Compared to controls, increased concentrations of ADMA were observed in cardio-embolic infarction (0.55 ± 0.08; p < 0.001; n = 71), and TIA (0.54 ± 0.05; p < 0.001; n = 31), but not in non-cardio-embolic infarction (0.51 ± 0.07; p = 0.56; n = 239) and haemorrhagic stroke (0.51 ± 0.11; p = 0.77; n = 22). In multivariate logistic regression models, CVD increased across quartiles of ADMA in all subgroups, but this association was only significant in the TIA group (odds ratio for highest versus lowest quartile 13.1; 95% CI: 2.9–58.6; p trend 0.001) A decreased arginine/ADMA ratio was significantly associated with CVD in the entire study population (p < 0.01). Our results indicate that ADMA is a weak independent marker for acute stroke and a strong marker for TIA and that relative arginine deficiency, measured as the l-arginine/ADMA ratio, is present in acute CVD.

    Emneord
    Asymmetric dimethylarginine; Arginine; Atherosclerosis; Stroke; TIA
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-14009 (URN)10.1016/j.atherosclerosis.2005.06.033 (DOI)
    Tilgjengelig fra: 2006-09-28 Laget: 2006-09-28 Sist oppdatert: 2009-06-08
    4. Asymmetric dimethylarginine and polymorphisms of fatty acid-binding protein 2 and endothelial nitric oxide synthase genes in carotid atherosclerosis
    Åpne denne publikasjonen i ny fane eller vindu >>Asymmetric dimethylarginine and polymorphisms of fatty acid-binding protein 2 and endothelial nitric oxide synthase genes in carotid atherosclerosis
    Vise andre…
    Manuskript (Annet vitenskapelig)
    Identifikatorer
    urn:nbn:se:liu:diva-14010 (URN)
    Tilgjengelig fra: 2006-09-28 Laget: 2006-09-28 Sist oppdatert: 2010-01-13
  • 58.
    Wårdell, Karin
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan.
    Kefalopoulou, Zinovia
    Unit of Functional Neurosurgery, Institute of Neurology, University College London, London, UK.
    Diczfalusy, Elin
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska högskolan.
    Andersson, Mats
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Tekniska högskolan.
    Åström, Mattias
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan.
    Limousin, Patricia
    Unit of Functional Neurosurgery, Institute of Neurology, University College London, London, UK.
    Zrinzo, Ludvic
    Unit of Functional Neurosurgery, Institute of Neurology, University College London, London, UK.
    Hariz, Marwan
    Unit of Functional Neurosurgery, Institute of Neurology, University College London, London, UK / Department of Clinical Neuroscience, Umeå University, Umeå, Sweden.
    Deep Brain Stimulation of the Pallidum Internum for Gilles de la Tourette Syndrome: A Patient-Specific Model-Based Simulation Study of the Electric Field2015Inngår i: Neuromodulation (Malden, Mass.), ISSN 1094-7159, E-ISSN 1525-1403, nr 2, s. 90-96Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives

    The aim of this study was to investigate the deep brain stimulation (DBS) electric field distribution in proton-density MRI scans visualizing the globus pallidus internus (GPi) of patients with Gilles de la Tourette syndrome (GTS), along with its relation to the anatomy.

    Methods

    Patient-specific brain tissue models (n = 7) with bilateral DBS electrodes in the GPi were set up using the finite element method in five patients who had undergone stereotactic proton-density MRI-guided surgery and showed variable improvement with DBS. Simulations (n = 27) of the electric field were performed and the results visualized on the respective preoperative stereotactic MRI scans. The mean electric field volumes (n = 81) within the 0.1, 0.15, and 0.2 V/mm isosurfaces were calculated and compared with the anatomy.

    Results

    Visualization of the simulated electric field confirmed that the anteromedial limbic GPi was the main stimulated target for four of the patients and the posteromedial sensorimotor GPi for one. Larger volumes extended asymmetrically, with parts of fields stretching into the lamina between GPi and globus pallidus externus and into the internal capsule. There was a high correlation (r = 0.994, n = 54) between volumes and brain sides, but with a systematic shift toward the right side, especially for the larger volumes. Simulations with homogeneous tissue models showed no differences.

    Conclusions

    Patient-specific DBS electric field simulations in the GPi as visualized on proton-density MR scans can be implemented in patients with GTS. Visualization of electric fields together with stereotactic thin-slice MRI can provide further support when predicting anatomical structures possibly influenced by DBS in this complex disorder.

  • 59.
    Zetterqvist, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    Non-Suicidal Self-Injury in Swedish Adolescents: Prevalence, Characteristics, Functions and Associations With Childhood Adversities2014Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Non-suicidal self-injury (NSSI), such as intentionally cutting, burning or hitting oneself, is a behavior with potentially detrimental consequences and empirical studies are necessary to gain knowledge of how to prevent NSSI in adolescents. The aims of this thesis were to investigate the prevalence, methods, characteristics and functions of NSSI in a large community sample of Swedish adolescents, and to examine the relationship between NSSI and adverse life events and trauma symptoms. All empirical studies had a cross-sectional design and were based on 3,097 adolescents in the county of Östergötland, aged 15-17 years, in their first year of high school. Participating school classes were selected through a randomization process and administered self-report questionnaires.

    In study I (n = 3,060) a single item NSSI question resulted in a prevalence rate of 17.2%, while 35.6% of adolescents reported having engaged in NSSI at least once during the past year when given a checklist. The most commonly reported type of NSSI in this sample was “bit yourself”, followed by “hit yourself on purpose”, “erased your skin” and “cut or carved on your skin”. Applying the proposed DSM-5 diagnostic criteria of NSSI resulted in a prevalence rate of 6.7%. Results in study II (n = 2,964) showed that after controlling for gender, parental occupation and living conditions, adolescents with no self-injurious behavior reported the lowest level of adversities and trauma symptoms, while adolescents with both NSSI and suicide attempts (5.7%) reported the highest levels compared to those with only NSSI or a suicide attempt. Adolescents reporting frequent NSSI reported more adversities and trauma symptoms than those with less frequent NSSI. Automatic functions, such as affect regulation, self-punishment and feeling-generation, were the most commonly reported functions of NSSI. Attempts in study I to confirm Nock and Prinstein’s (2004) four-factor model of underlying factors of NSSI functions resulted in a close to acceptable fit. An attempt to refine the factor analysis on this community sample of Swedish adolescents, using Mplus with cross-validation, was made in study III (n = 836). An exploratory factor analysis resulted in a three-factor model (social influence, automatic functions and non-conformist peer identification), which was validated in confirmatory analysis. In order to adhere more closely to learning theory and the concept of negative and positive reinforcement, the third factor was then split into two factors, resulting in a four-factor model (social influence, automatic functions, peer identification and avoiding demands), which showed excellent fit to the data in the confirmatory factor analysis. Study IV (n = 816) showed that NSSI frequency, gender (female), self-reported experience of emotional and physical abuse, having made a suicide attempt, prolonged illness or handicap and symptoms of depression and dissociation were significant predictors in the final model of the automatic functions, indicating that these variables are important in understanding the mechanisms underlying the need to engage in NSSI to regulate emotions, generate feelings, gain control or to self-punish. Symptoms of depression and dissociation mediated the relationship between sexual, physical and emotional abuse and the automatic  functions. Furthermore, frequency of NSSI, gender, emotional abuse, prolonged illness or handicap and symptoms of depression uniquely predicted automatic functions but not social functions. Self-reported experience of physical abuse, having made a suicide attempt, symptoms of anxiety and dissociation were significant in the final model of social functions, i.e., performing NSSI to influence or  communicate with others, to avoid demands or to identify with peers. Of these, symptoms of anxiety were uniquely associated with social functions. Symptoms of anxiety and dissociation mediated the relationship between physical abuse and social functions of NSSI.

    Taken together, this thesis has shown that NSSI is prevalent in Swedish adolescents and findings contribute to the discussion of a potential NSSI diagnosis. It is important to consider the effect of different types of negative life events and trauma symptoms in relation to NSSI in adolescents. Assessing the specific reinforcing functions of NSSI and the underlying factor structure can be helpful in developing functionally relevant individualized treatment.

    Delarbeid
    1. Prevalence and Function of Non-Suicidal Self-Injury (NSSI) in a Community Sample of Adolescents, Using Suggested DSM-5 Criteria for a Potential NSSI Disorder
    Åpne denne publikasjonen i ny fane eller vindu >>Prevalence and Function of Non-Suicidal Self-Injury (NSSI) in a Community Sample of Adolescents, Using Suggested DSM-5 Criteria for a Potential NSSI Disorder
    2013 (engelsk)Inngår i: Journal of Abnormal Child Psychology, ISSN 0091-0627, E-ISSN 1573-2835, Vol. 41, nr 5, s. 759-773Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Previous prevalence rates of non-suicidal self-injury (NSSI) in adolescents have varied considerably. In the present cross-sectional study, prevalence rates, characteristics and functions of NSSI were assessed in a large randomized community sample consisting of 3,060 (50.5 % female) Swedish adolescents aged 15-17 years. The suggested criteria for NSSI disorder in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, (DSM-5) were used to assess prevalence rates with the aim of arriving at a more precise estimate. Out of the whole sample, 1,088 (35.6 %) adolescents (56.2 % female) reported at least one episode of NSSI during the last year, of which 205 (6.7 %) met suggested DSM-5 criteria for a potential NSSI disorder diagnosis. The NSSI disorder diagnosis was significantly more common in girls (11.1 % vs. 2.3 %, χ (2) (1, N = 3046) = 94.08, p < 0.001, cOR = 5.43, 95 % CI [3.73, 7.90]). The NSSI disorder group consisted of significantly more smokers and drug users compared to adolescents with NSSI that did not meet DSM-5 criteria for NSSI disorder, and also differed concerning demographic variables. A confirmatory factor analysis (CFA) was conducted on reported functions of NSSI, with the aim of validating Nock and Prinstein's (Journal of Consulting and Clinical Psychology 72:885-890, 2004, Journal of Abnormal Psychology 114:140-146, 2005) four-factor model on a Swedish community sample, resulting in a close to acceptable fit. A two-factor model (social and automatic reinforcement) resulted in a slightly better fit. The most frequently reported factors were positive and negative automatic reinforcement. A majority of functions were significantly more often reported by girls than boys. The implications of the suggested DSM-5 criteria and reported functions are discussed.

    sted, utgiver, år, opplag, sider
    Springer, 2013
    Emneord
    Non-suicidal self-injury disorder, DSM-5, Prevalence, Function, Adolescents
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-91375 (URN)10.1007/s10802-013-9712-5 (DOI)000320279900007 ()23344701 (PubMedID)
    Tilgjengelig fra: 2013-04-23 Laget: 2013-04-23 Sist oppdatert: 2018-04-07
    2. A Comparison of Adolescents Engaging in Self-Injurious Behaviors With and Without Suicidal Intent: Self-Reported Experiences of Adverse Life Events and Trauma Symptoms
    Åpne denne publikasjonen i ny fane eller vindu >>A Comparison of Adolescents Engaging in Self-Injurious Behaviors With and Without Suicidal Intent: Self-Reported Experiences of Adverse Life Events and Trauma Symptoms
    2013 (engelsk)Inngår i: Journal of Youth and Adolescence, ISSN 0047-2891, E-ISSN 1573-6601, Vol. 42, nr 8, s. 1257-1272Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Research comparing adolescents engaging in suicidal and non-suicidal self-injury (NSSI), both separately and in combination, is still at an early stage. The purpose of the present study was to examine overlapping and distinguishable features in groups with different types of self-injurious behaviors, using a large community sample of 2,964 (50.6 % female) Swedish adolescents aged 15-17 years. Adolescents were grouped into six categories based on self-reported lifetime prevalence of self-injurious behaviors. Of the total sample, 1,651 (55.7 %) adolescents reported no self-injurious behavior, 630 (21.2 %) reported NSSI 1-4 times, 177 (6.0 %) reported NSSI 5-10 times, 311 (10.5 %) reported NSSI a parts per thousand yen 11 times, 26 (0.9 %) reported lifetime prevalence of suicide attempt and 169 (5.7 %) adolescents reported both NSSI and suicide attempt. After controlling for gender, parental occupation and living conditions, there were significant differences between groups. Pairwise comparisons showed that adolescents with both NSSI and suicide attempt reported significantly more adverse life events and trauma symptoms than adolescents with only NSSI, regardless of NSSI frequency. The largest differences (effect sizes) were found for interpersonal negative events and for symptoms of depression and posttraumatic stress. Adolescents with frequent NSSI reported more adversities and trauma symptoms than those with less frequent NSSI. There were also significant differences between all the NSSI groups and adolescents without any self-injurious behavior. These findings draw attention to the importance of considering the cumulative exposure of different types of adversities and trauma symptoms when describing self-injurious behaviors, with and without suicidal intent.

    sted, utgiver, år, opplag, sider
    Springer, 2013
    Emneord
    Non-suicidal self-injury, Suicide, Adolescents, Adverse life events, Trauma symptoms
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-96719 (URN)10.1007/s10964-012-9872-6 (DOI)000321973800012 ()
    Tilgjengelig fra: 2013-08-23 Laget: 2013-08-23 Sist oppdatert: 2017-12-06bibliografisk kontrollert
    3. Functions of Nonsuicidal Self-Injury: Exploratory and Confirmatory Factor Analyses in a Large Community Sample of Adolescents
    Åpne denne publikasjonen i ny fane eller vindu >>Functions of Nonsuicidal Self-Injury: Exploratory and Confirmatory Factor Analyses in a Large Community Sample of Adolescents
    2015 (engelsk)Inngår i: Psychological Assessment, ISSN 1040-3590, E-ISSN 1939-134X, Vol. 27, nr 1, s. 302-313Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Given that nonsuicidal self-injury (NSSI) is prevalent in adolescents, structured assessment is an essential tool to guide treatment interventions. The Functional Assessment of Self-Mutilation (FASM) is a self-report scale that assesses frequency, methods, and functions of NSSI. FASM was administered to 3,097 Swedish adolescents in a community sample. With the aim of examining the underlying factor structure of the functions of FASM in this sample, the adolescents with NSSI who completed all function items (n = 836) were randomly divided into 2 subsamples for cross-validation purposes. An exploratory factor analysis (EFA) was followed by a confirmatory factor analysis (CFA) using the mean and variance adjusted weighted least squares (WLSMV) estimator in the Mplus statistical modeling program. The results of the EFA suggested a 3-factor model (social influence, automatic functions, and nonconformist peer identification), which was supported by a good fit in the CFA. Factors differentiated between social/interpersonal and automatic/intrapersonal functions. Based on learning theory and the specific concepts of negative and positive reinforcement, the nonconformist peer identification factor was then split into 2 factors (peer identification and avoiding demands). The resulting 4-factor model showed an excellent fit. Dividing social functions into separate factors (social influence, peer identification, and avoiding demands) can be helpful in clinical practice, where the assessment of NSSI functions is an important tool with direct implications for treatment.

    sted, utgiver, år, opplag, sider
    American Psychological Association (APA), 2015
    Emneord
    Non-suicidal self-injury, assessment, adolescents, functions, factor analysis
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-110420 (URN)10.1037/pas0000034 (DOI)25558962 (PubMedID)
    Merknad

    At the time for thesis presentation publication was in status: Manuscript

    Tilgjengelig fra: 2014-09-11 Laget: 2014-09-11 Sist oppdatert: 2018-04-07bibliografisk kontrollert
    4. A cross-sectional study of adolescent non-suicidal self-injury: support for a specific distress-function relationship
    Åpne denne publikasjonen i ny fane eller vindu >>A cross-sectional study of adolescent non-suicidal self-injury: support for a specific distress-function relationship
    2014 (engelsk)Inngår i: Child and Adolescent Psychiatry and Mental Health, ISSN 1753-2000, E-ISSN 1753-2000, Vol. 8, nr 23Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    BACKGROUND: This study has investigated the specific relationship between childhood adversities, individual trauma symptoms and the functions of non-suicidal self-injury (NSSI). The aim was to examine whether different self-reported adverse experiences and trauma symptoms predict the need to engage in NSSI, either to regulate emotions or to communicate with and influence others.

    METHOD: The participants were a community sample of 816 adolescents aged 15-17 years with NSSI. Hierarchical multiple regression was used, controlling for NSSI frequency and gender. The dependent variables were the automatic and social functions of NSSI, respectively. The predictors entered in the model were several different maltreatment and adversity experiences as well as individual trauma symptoms. Mediation analyses were also performed using the bootstrapping method with bias-corrected confidence estimates.

    RESULTS: Frequency of NSSI, gender (female), emotional abuse, prolonged illness or handicap during upbringing and symptoms of depression uniquely predicted the automatic functions of NSSI in the final regression model, but not the social functions. Symptoms of anxiety uniquely predicted social but not automatic functions. Having experienced physical abuse, having made a suicide attempt and symptoms of dissociation were significant predictors in both final models. The model for automatic functions explained more of the variance (62%) than the social model (28%). The relationship between childhood emotional, physical and sexual abuse and performing NSSI for automatic reasons was mediated by symptoms of depression and dissociation. The relationship between physical abuse and the social functions of NSSI was mediated by symptoms of anxiety and dissociation.

    CONCLUSIONS: It is important to understand the specific context in which NSSI has developed and is maintained. Experiences of emotional abuse and symptoms of depression could guide clinical work in the direction of emotion regulation skills since in this study these variables were uniquely associated with the need to engage in NSSI to regulate emotions, to self-punish or to generate feelings. The presence of physical abuse, a suicide attempt and symptoms of dissociation could alert clinicians to a broad treatment approach since they were associated with performing NSSI to regulate both social and automatic experiences.

    sted, utgiver, år, opplag, sider
    BioMed Central, 2014
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-110419 (URN)10.1186/1753-2000-8-23 (DOI)25110519 (PubMedID)
    Tilgjengelig fra: 2014-09-11 Laget: 2014-09-11 Sist oppdatert: 2017-12-05bibliografisk kontrollert
  • 60.
    Zsigmond, Peter
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Sinnescentrum, Neurokirurgiska kliniken US.
    Nord, Maria
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet.
    Kullman, Anita
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för mikrobiologi och molekylär medicin. Linköpings universitet, Hälsouniversitetet.
    Diczfalusy, Elin
    Linköpings universitet, Institutionen för medicinsk teknik, Biomedicinsk instrumentteknik. Linköpings universitet, Tekniska högskolan.
    Wårdell, Karin
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan. Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV.
    Dizdar (Dizdar Segrell), Nil
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Neurologiska kliniken.
    Neurotransmitter levels in basal ganglia during levodopa and deep brain stimulation treatment in Parkinson’s disease2014Inngår i: Neurology and Clinical Neuroscience, ISSN 2049-4173, Vol. 2, nr 5, s. 149-155Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background The mechanism by which deep brain stimulation of the nucleus subthalamicus improves Parkinson’s disease symptoms remains unclear. In a previous perioperative study, we showed that there might be alterations of neurotransmitter levels in the globus pallidum interna during deep brain stimulation of the nucleus subthalamicus. Aim In this study, we examined whether deep brain stimulation of the nucleus subthalamicus and levodopa infusion interact and affect the levels of neurotransmitters. Methods Five patients with advanced Parkinson’s disease took part in the study. During subthalamic nucleus surgery, microdialysis catheters were inserted bilaterally in the globus pallidum interna and unilaterally in the right putamen. A study protocol was set up and was followed for 3 days. Levodopa infusion with and without concomitant bilateral deep brain stimulation of the nucleus subthalamicus was also carried out. Results The putaminal dopamine levels increased during deep brain stimulation of the nucleus subthalamicus. In addition, an increase of gamma amino buturic acid concentrations in the globus pallidum interna during deep brain stimulation of the nucleus subthalamicus and during levodopa infusion was found. Conclusions These findings provide evidence that the subthalamic nucleus has a direct action on the substantia nigra pars compacta, and that deep brain stimulation of the nucleus subthalamicus might indirectly release putaminal dopamine. There is also evidence that deep brain stimulation of the nucleus subthalamicus interferes with levodopa therapy resulting in higher levels of levodopa in the brain, explaining why it is possible to decrease levodopa medication after deep brain stimulation surgery.

  • 61.
    Zuiderent-Jerak, Teun
    et al.
    Linköpings universitet, Institutionen för tema, Tema teknik och social förändring. Linköpings universitet, Filosofiska fakulteten.
    Grit, Kor
    Department of Health Policy and Management, Erasmus University, Rotterdam.
    Grinten, Tom van der
    Department of Health Policy and Management, Erasmus University, Rotterdam.
    Critical composition of public values: on the enactment and disarticulation of what counts in health-care markets2015Inngår i: Value practices in the life sciences and medicine / [ed] Isabelle Dussauge, Claes-Fredrik Helgesson, Francis Lee, Oxford: Oxford University Press, 2015, s. 119-135Kapittel i bok, del av antologi (Fagfellevurdert)
  • 62.
    Åkerman, Linda
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Medicinska fakulteten.
    Aspects of the Pre-Diabetic Period in Type 1 Diabetes2016Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Type 1 diabetes (T1D) is an autoimmune disease characterized by insulin deficiency, due to immune-mediated destruction of beta cells. Current knowledge regarding the period preceding disease onset comes, to a large extent, from studying risk cohorts based on relatives of T1D-patients, as they have an increased disease risk. Among T1D patients in general, however, few have the disease in their immediate family. It is therefore important to study risk cohorts from the general population as well. An ongoing autoimmune reaction can often be seen in the blood long before disease onset, by detection of autoantibodies directed towards beta cell antigens. By autoantibody screening among participants in the ABIS (All Babies in the South-east of Sweden) cohort, we could identify a group of children from the general population with increased risk for T1D, positive for multiple autoantibodies. They were enrolled in a 2-year prospective follow-up aiming to characterize the prediabetic period and to identify factors indicative of progression/non-progression to T1D. We assessed glucose homeostasis and autoantibody titers over time, and searched for risk-biomarkers by analyzing the expression of immune-related genes (Th1-Th2-Th3) in peripheral blood mononuclear cells (PBMC) from these children, in comparison to healthy children and newly diagnosed T1D patients. In the same groups we also compared serum micro RNA (miRNA) profiles, knowing that miRNA molecules have desirable biomarker properties. We found that two specific autoantibodies, IA2A and ZnT8A, were detected at higher concentrations in risk-individuals who progressed to overt T1D during or after the follow-up period, compared to those who still have not. We also observed disturbed glucose homeostasis long before onset in the progressors, but it was seen among those who remain symptom free as well. Further, we found support for the possible role of insulin resistance as an accelerator of the disease process. For gene expression and serum miRNA, few differences were observed between risk-individuals and healthy children overall. However, for PBMC gene expression and serum miRNA both, there were associations to beta cell function and glucose homeostasis, and for miRNA also to islet autoantibodies. Although specific profiles for prediction of disease onset or identification of risk-individuals could not be found, these results are interesting and deserve to be evaluated further. As part of another sub-study within ABIS, the effects of physical activity on glucose homeostasis were assessed in healthy schoolchildren. The level of physical activity, measured by pedometers, was related to insulin resistance and beta cell-stress, and decreased physical activity was associated with increased insulin resistance and load on the insulin-producing beta cells, already at school-age.

    Delarbeid
    1. Low C-peptide levels and decreased expression of TNF and CD45 in children with high risk of type 1 diabetes
    Åpne denne publikasjonen i ny fane eller vindu >>Low C-peptide levels and decreased expression of TNF and CD45 in children with high risk of type 1 diabetes
    2013 (engelsk)Inngår i: Clinical Immunology, ISSN 1521-6616, E-ISSN 1521-7035, Vol. 148, nr 1Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Type 1 diabetes (T1D) patients have numeral and functional defects in peripheral immune cells, but the pre-diabetic period is fairly uncharacterized. Our aim was to analyze expression of immunological markers in T1D high risk children and relate it to clinical/immunological parameters. Children from ABIS (All Babies in Southeast Sweden) with greater than= 2 diabetes related autoantibodies were considered at high risk. Age-matched controls and new-onset T1D patients were included. Expression of genes related to immune cell function and different arms of the immune system was assessed in peripheral blood mononuclear cells using PCR array. Risk children had lower TNF and CD45, and although there were few differences between the groups, expression of many genes differed when comparing children with regard to residual insulin secretion. Hence, expression of immune related genes seemed related not only to the autoimmune process but rather to residual beta-cell function, which was decreased already during the pre-diabetic phase.

    sted, utgiver, år, opplag, sider
    Elsevier, 2013
    Emneord
    Type 1 diabetes; Gene expression; PBMC; T1D high risk; T1D autoantibodies; PCR array
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-96458 (URN)10.1016/j.clim.2013.03.011 (DOI)000320427300002 ()
    Tilgjengelig fra: 2013-08-23 Laget: 2013-08-20 Sist oppdatert: 2017-12-06
    2. Physical Activity, Blood Glucose and C-Peptide in Healthy School-Children, a Longitudinal Study
    Åpne denne publikasjonen i ny fane eller vindu >>Physical Activity, Blood Glucose and C-Peptide in Healthy School-Children, a Longitudinal Study
    2016 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 6, s. e0156401-Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Aim To further elucidate the relationship between physical activity and several risk factors for development of diabetes (glucose, C-peptide and obesity) over time. Methods A prospective longitudinal study where physical activity was measured on 199 children from Kalmar and Linkoping at age 8, and the same 107 children from Linkoping again at age 12. Anthropometric data was collected and blood was analyzed for C-peptide and f-glucose. The children in the study were representative for the general Swedish child population, and on an average lean. Results High physical activity was related to lower C-peptide at age 8 and 12. This correlation was especially pronounced in boys, who also were more physically active than girls at both time points. The association seen at 8 years of age was similar at age 12 in most children. Children with higher BMI Z-Score had a higher fasting C-peptide (age 12) but linear regression showed that children with more steps per day were less likely to have a higher fasting C-peptide irrespective of BMI. Longitudinal follow-up showed that a decrease in physical activity increased insulin resistance and beta-cell load. Conclusions Already in young children, physical activity improves insulin sensitivity and decreases the need of C-peptide over time. This seems to become even more pronounced with increasing age when children are followed longitudinally. Low physical activity increases the load on insulin producing beta-cells, might increase the risk for both type 1- and 2 diabetes.

    sted, utgiver, år, opplag, sider
    PUBLIC LIBRARY SCIENCE, 2016
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-130132 (URN)10.1371/journal.pone.0156401 (DOI)000377561000012 ()27270732 (PubMedID)
    Merknad

    Funding Agencies|Swedish Child Diabetes Foundation (Barndiabetesfonden); Novo Nordisk Foundation; Research Council of South-east Sweden (FORSS); Swedish Research Council [K2005-72X-11242-11A]; ALF/County Council of Ostergotland

    Tilgjengelig fra: 2016-07-12 Laget: 2016-07-11 Sist oppdatert: 2017-11-28
  • 63.
    Åsberg, Cecilia
    et al.
    Linköpings universitet, Institutionen för tema, Tema Genus. Linköpings universitet, Filosofiska fakulteten.
    Birke, Lynda
    University Chester, UK.
    Biology is a feminist issue: Interview with Lynda Birke2010Inngår i: The European Journal of Women's Studies, ISSN 1350-5068, E-ISSN 1461-7420, Vol. 17, nr 4, s. 413-423Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    This is an interview with Professor Lynda Birke (University of Chester, UK), one of the key figures of feminist science studies. She is a pioneer of feminist biology and of materialist feminist thought, as well as of the new and emerging field of hum-animal studies (HAS). This interview was conducted over email in two time periods, in the spring of 2008 and 2010. The format allowed for comments on previous writings and an engagement in an open-ended dialogue. Professor Birke talks about her key arguments and outlooks on a changing field of research. The work of this English biologist is typical of a long and continuous feminist engagement with biology and ontological matters that reaches well beyond the more recently articulated material turn of feminist theory. It touches upon feminist issues beyond the usual comfort zones of gender constructionism and human-centred research. Perhaps less recognized than for instance the names of Donna Haraway or Karen Barad, Lynda Birkes oeuvre is part of the same long-standing and twofold critique from feminist scholars qua trained natural scientists. On the one hand, theirs is a powerful critique of biological determinism; on the other, an acutely observed contemporary critique of how merely cultural or socially reductionist approaches to the effervescently lively and biological might leave the corporeal, environmental or non-human animal critically undertheorized within feminist scholarship. In highlighting the work and arguments of Lynda Birke, it is hoped here to provide an accessible introduction to the critical questions and challenges that circumvent contemporary discussions within feminist technoscience as theory and political practice.

  • 64.
    Åström, Mattias
    et al.
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan. Sapiens Steering Brain Stimulation BV, NL-5656 Eindhoven, Netherlands.
    Diczfalusy, Elin
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan.
    Martens, Hubert
    Sapiens Steering Brain Stimulation B.V., Eindhoven, The Netherlands.
    Wårdell, Karin
    Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska högskolan.
    Relationship between Neural Activation and Electric Field Distribution during Deep Brain Stimulation2015Inngår i: IEEE Transactions on Biomedical Engineering, ISSN 0018-9294, E-ISSN 1558-2531, Vol. 62, nr 2, s. 664-72Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Models and simulations are commonly used to study deep brain stimulation (DBS). Simulated stimulation fields are often defined and visualized by electric field isolevels or volumes of tissue activated (VTA). The aim of the present study was to evaluate the relationship between stimulation field strength as defined by the electric potential V, the electric field E, and the divergence of the electric field ∇(2) V, and neural activation. Axon cable models were developed and coupled to finite-element DBS models in three-dimensional (3-D). Field thresholds ( VT , ET, and ∇(2) VT ) were derived at the location of activation for various stimulation amplitudes (1 to 5 V), pulse widths (30 to 120 μs), and axon diameters (2.0 to 7.5 μm). Results showed that thresholds for VT and ∇(2) VT were highly dependent on the stimulation amplitude while ET were approximately independent of the amplitude for large axons. The activation field strength thresholds presented in this study may be used in future studies to approximate the VTA during model-based investigations of DBS without the need of computational axon models.

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