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  • 201.
    Adolfsson, Lars
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Östergötlands Läns Landsting, Ortopedicentrum, Ortopedkliniken Linköping.
    Open vs. arthroscopic synovectomy of the wrist2006Inngår i: Excerpta Medica: International Congress Series, ISSN 0531-5131, E-ISSN 1873-6157, Vol. 1295, s. 56-62Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Synovectomy may be considered for the treatment of chronic wrist arthritis. The indications for wrist synovectomy are, however, not clearly defined. Open synovectomy has been reported to provide good pain relief for a relatively long time but can be associated with loss of mobility. Arthroscopic synovectomy seems equally reliable in terms of symptom reduction and no adverse effects have been reported. © 2006 Elsevier B.V. All rights reserved.

  • 202.
    Adolfsson, Lars
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Hand och plastikkirurgi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Hand- och plastikkirurgiska kliniken US.
    Lysholm, J
    Ortopedklin Boden.
    Nettelblad, Hans
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för biomedicin och kirurgi, Hand och plastikkirurgi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Hand- och plastikkirurgiska kliniken US.
    Adverse effects of extensive clavicular resections and a suggessted method of reconstruction.1999Inngår i: Journal of shoulder and elbow surgery, ISSN 1058-2746, E-ISSN 1532-6500, Vol. 8, s. 361-365Artikkel i tidsskrift (Fagfellevurdert)
  • 203.
    Adolfsson, Lars
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Nestorson, Jens
    Östergötlands Läns Landsting, Ortopedicentrum, Ortopedkliniken Linköping.
    The Kudo humeral component as primary hemiarthroplasty in distal humeral fractures2012Inngår i: Journal of shoulder and elbow surgery, ISSN 1058-2746, E-ISSN 1532-6500, Vol. 21, nr 4, s. 451-455Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Treatment of intra-articular fractures of the distal humerus in the elderly is challenging. In patients with very distal fractures and severe comminution, primary arthroplasty has been advocated. Recently, a few reports have described promising results of hemiarthroplasty. This study describes the medium-term results of using the Kudo humeral implant (Biomet Ltd, Bridgend, U. K.) as replacement of the distal humerus. less thanbrgreater than less thanbrgreater thanMaterial and methods: Eight women (mean age, 79 years) were treated. Follow-up was conducted at a mean of 4 years after the procedure and consisted of the Mayo Elbow Performance Score (MEPS), radiographic images, and range of motion (ROM). less thanbrgreater than less thanbrgreater thanResults: All patients had a good or excellent outcome according to the MEPS. Mean ROM was 31 degrees to 126 degrees. Radiographic signs of attrition of the ulna were observed in 3 patients but did not correlate with the functional outcome. A periprosthetic fracture occurred in 1 patient 3 years after the index operation, and ROM was unsatisfactory in 1 patient. No other complications were observed. less thanbrgreater than less thanbrgreater thanConclusion: The use of the Kudo humeral implant as a hemiarthroplasty resulted in a reasonable functional outcome in the medium-term, but the radiographic signs of attrition suggest that the implant is not recommended as a hemiprosthesis.

  • 204.
    Adolfsson, Lars
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Nestorson, Jens
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Scheer, Johan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för Kirurgi, Ortopedi och Onkologi. Linköpings universitet, Medicinska fakulteten.
    Extensive soft tissue lesions in redislocated after simple elbow dislocations2017Inngår i: Journal of shoulder and elbow surgery, ISSN 1058-2746, E-ISSN 1532-6500, Vol. 26, nr 7, s. 1294-1297Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: The majority of simple elbow dislocations (no associated fractures) can be treated nonoperatively with a short period of immobilization followed by guided aftercare. This case series describes the soft tissue injuries in a rare subset of patients in whom the elbow redislocated despite adequate immobilization. Methods: During a 6-year period, 8 patients were identified. They were all treated with reduction and casting in 90 degrees of flexion or more. At 1 week of follow-up, redislocation had occurred in all patients and open soft tissue repair was performed. The injuries were documented and the patients were followed up clinically and with radiographs. Results: Extensive soft tissue injuries, including both collateral ligament injuries and muscle origin avulsions from either or both sides, were found in all patients. The functional result at follow-up was satisfactory in all patients. Conclusion: Vast soft tissue injuries including both collateral ligaments and muscle origins should be expected in the event of early severe instability of a dislocated elbow joint. (C) 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. All rights reserved.

  • 205.
    Adolfsson, Lars
    et al.
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Ortopedi och Idrottsmedicin. Östergötlands Läns Landsting, Ortopedicentrum, Ortopedkliniken Linköping.
    Povlsen, B
    Arthroscopic findings in wrists with severe post-traumatic pain despite normal standard radiographs2004Inngår i: Journal of Hand Surgery - British and European Volume, ISSN 0266-7681, E-ISSN 1532-2211, Vol. 29 B, nr 3, s. 208-213Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study assessed the role of diagnostic arthroscopy following a wrist injury in patients with normal standard radiographs, an unclear clinical diagnosis and persistent severe pain at 4 to 12 weeks. Forty-three patients were included after conservative management had failed to improve their wrist pain so that a stability test could be performed satisfactorily and underwent arthroscopy within 12 weeks. Arthroscopy revealed recent pathology in 41 wrists, of which 17 had significant ligament lesions that might have benefited from acute repair. We conclude that patients with marked persistent post-traumatic symptoms despite conservative management are likely to have sustained ligament injuries despite normal radiographs. We therefore recommend that under these circumstances an arthroscopy is carried out within 4 weeks if the patient and surgeon wish to acutely repair significant ligament injuries.

  • 206. Adolfsson, L.E.
    et al.
    Nettelblad, Hans
    Linköpings universitet, Hälsouniversitetet. Linköpings universitet, Institutionen för klinisk och experimentell medicin, Kirurgi. Östergötlands Läns Landsting, Rekonstruktionscentrum, Hand- och plastikkirurgiska kliniken US.
    Radial nerve entrapment in the upper arm as a cause of lateral arm pain: A report of four cases2001Inngår i: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery, ISSN 2000-656X, E-ISSN 2000-6764, Vol. 35, nr 2, s. 217-220Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Four patients with no history of trauma presented with lateral arm pain, local tenderness, and a tingling sensation at the distal end of the arm when the radial nerve was percussed in the mid-third of the upper arm (Tinel's sign), but no clinical or subjective signs of muscular weakness. They were treated by decompression of the radial nerve in the fibrous canal proximal to the lateral intermuscular septum. Three of the patients had a complete or pronounced reduction in pain, while the fourth had only a slight improvement. Non-traumatic radial nerve entrapment in the upper arm may be the cause of lateral arm pain without clinical signs of muscular weakness.

  • 207.
    Adolfsson, Per
    Linköpings universitet, Institutionen för medicin och vård, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Regulatory importance of cyclic nucleotides in smooth muscle growth of the urogenital tract2001Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Smooth muscle hyperplasia/hypertrophy is, if not responsible for, so at least involved in those diseases, which impair life quality for most people in today's society.

    This thesis, presents a pharmacological investigation, related to the regulatory role of cyclic nucleotides, of smooth muscle hyperplasia/hypeitrophy in human uterine leiomyoma and benign prostate hyperplasia (BPH).

    Four main aspects, with cAMP as a connecting thought, have been analyzed, namely expression and characterization of the adrenergic receptors (AR), determination of adenylyl cyclase (AC)- and phosphodiesterase (PDE)-activity, and finally the connection between mentioned issues and proliferation of cultured smooth muscle cells (smc).

    In the frrst paper, characterization of the a 2-adrenergic receptor (az-AR) subtypes in human myometrium at term pregnancy was examined by combining radioligand binding-studies with reverse transcriptase-polymerase chain reaction (RT-PCR). Results demonstrated a significant eo-expression of α2A and α2B, and a weak indication of the α2C-AR, which however was identified at the mRNA level by the RT-PCR analysis.

    In the next investigatio~ smooth muscle tissue of human uterine leiomyoma (benign smooth muscle tumor) was compared with surrounding myometrial tissue (control). The expression of AR, AC- and PDE-activity was analyzed, as well as the effect of cAMP with respect to growth regulation of cultured leiomyoma smc. Primarily, a significantly reduced ß2-AR expression and AC-activity was detected in leiomyoma compared to control tissue, whereas the PDE-activity was approximately 100% higher. In addition, the α2-AR population in leiomyoma was slightly increased. When cultured leiomyoma smc was treated with cAMP increasing agents as forskolin, an AC stimulating agent, or papaverin, a general PDE inhibitor, a considerable inhibition of DNA replication and protein synthesis was obtained.

    In the thh·d paper, a proliferation study was made on cultured benign prostate hyperplasia smc, were the mitogen effect of lysophosphatidic acid (LPA) and cAMP/cGMP increasing agents was investigated. LPA generated a dose-dependent mitogen response, which was efficiently inhibited, both by forskolin, and by papaverin. In addition, sildenafil (Viagra®), which serve as a potent and selective PDE5 inhibitor, also decreased the LPA mediated growth promotion in a dose dependent manner.

    The last study, demonstrate primarily the expression pattem of LPA receptors (Edg) in BPH smc. Further, the intracellular cAMP changes in LPA stimulated BPH smc and the proliferative effect of the LPA analogue sphingosine 1-phosphate (SIP) was considered. First, all Edg was identified with exception of Edg6. Moreover, the cAMP level was unchanged by LPA per se, whereas co-incubation with forskolin generated a rapid and transient response. Further, SIP generated a divergent response including a LPA equivalent mitogen effect at low concentrations whereas inhibition of DNA replication was obtained at higher concentrations.

    In summary, this project demonstrates that cyclic nucleotides inhibit smooth muscle hyperplasia/hypertrophy in the luogenital tract. These results also suggest that manipulation of cyclic nucleotide level using tissue specific PDE inhibitors might constitute a new therapeutic approach for hyperplasia/hypertrophy related diseases in the urogenital tract.

    Delarbeid
    1. Characterization of α2-Adrenoceptor Subtypes in Pregnant Human Myometrium
    Åpne denne publikasjonen i ny fane eller vindu >>Characterization of α2-Adrenoceptor Subtypes in Pregnant Human Myometrium
    1998 (engelsk)Inngår i: Gynecologic and Obstetric Investigation, ISSN 0378-7346, E-ISSN 1423-002X, Vol. 45, nr 3, s. 145-150Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The aim of the present investigation was to determine which subtypes of the α2-adrenoceptors are being expressed in the human pregnant myometrium at term pregnancy. In radioligand binding studies, the specific binding of [3H]rauwolscine to human myometrial membranes was specific and of high affinity with Kd of 2.8 ± 0.6 nM and Bmax of 95 ± 5 fmol/mg protein. Results from competition for the binding of [3H]rauwolscine using subtype-selective ligands, oxymetazoline (α2A-subptype), chlorpromazine (α2B-subtype) and prazosin (α2B-α2C-subtype), suggested that the α2A- and α2B-subtypes are being co-expressed. In order to examine if also the α2C-subtype is being expressed we used an optimal concentration of oxymetazoline or chlorpromazine which would block the high-affinity site, equivalent to the α2A- and α2B-subtype respectively. Competition curves of both oxymetazoline and chlorpromazine still showed a significantly better fit using a two-site model, suggesting that the α2C-subtype also is being expressed. The expression of α2C-subtype mRNA was confirmed using reverse transcription-polymerase chain reaction on mRNA isolated from myometrial biopsies.

    In conclusion, our results suggest that all three subtypes of α2-adrenoceptors are being coexpressed in the human myometrium at term pregnancy and that α2-expression is dominated by the α2A-subtype.

    Emneord
    α2-Adrenergic receptors, Subtype, Myometrium, Human, Pregnancy, [3H]rauwolscine, Reverse transcription-polymerase chain reaction
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-80081 (URN)10.1159/000009944 (DOI)
    Tilgjengelig fra: 2012-08-20 Laget: 2012-08-20 Sist oppdatert: 2017-12-07bibliografisk kontrollert
    2. Changes in β2-adrenoceptor expression and in adenylyl cyclase and phosphodiesterase activity in human uterine leiomyomas
    Åpne denne publikasjonen i ny fane eller vindu >>Changes in β2-adrenoceptor expression and in adenylyl cyclase and phosphodiesterase activity in human uterine leiomyomas
    2000 (engelsk)Inngår i: Molecular human reproduction, ISSN 1360-9947, E-ISSN 1460-2407, Vol. 6, nr 9, s. 835-842Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Uterine leiomyoma is a very common benign tumour with unclear pathophysiology in adult women. In the present study we have investigated the expression level of α2- and β2-adrenoceptors, and the adenylyl cyclase and phosphodiesterase activity in leiomyoma tissue compared with adjacent myometrium. Our results show that the α22-adrenoceptor ratio is increased in leiomyoma, due to a significant decrease in β2-adrenoceptor expression. These changes were not due to an increased innervation, as the tumour tissue was completely devoid of nerve fibres. Moreover, the adenylyl cyclase activity of leiomyoma membranes was found to be ~50% lower, whereas the phosphodiesterase activity was significantly increased (by ~100%). We found that stimulating an increase in intracellular cyclic AMP, by adenylyl cyclase activity through β2-adrenoceptors (isoprenaline), by direct enzyme activation (forskolin), or by inhibition of phosphodiesterase activity (papaverine), potently blocked both protein and DNA synthesis in cultured leiomyoma smooth muscle cells. Our results imply the adrenoceptors might be involved in, or a consequence of, leiomyoma growth. The results also suggest a new interesting approach for leiomyoma pharmacotherapy.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-25070 (URN)10.1093/molehr/6.9.835 (DOI)9500 (Lokal ID)9500 (Arkivnummer)9500 (OAI)
    Tilgjengelig fra: 2009-10-07 Laget: 2009-10-07 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    3. Lysophosphatidic acid stimulates proliferation of cultured smooth muscle cells from human BPH tissue: Sildenafil and papaverin generate inhibition
    Åpne denne publikasjonen i ny fane eller vindu >>Lysophosphatidic acid stimulates proliferation of cultured smooth muscle cells from human BPH tissue: Sildenafil and papaverin generate inhibition
    2002 (engelsk)Inngår i: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 51, nr 1, s. 50-58Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background The endogenous substance lysophosphatidic acid (LPA) has been found to generate proliferation of cultured smooth muscle cells (SMC). Therefore, the effect of LPA on human benign prostate hyperplasia (BPH) could be of interest.

    Methods The proliferative effect of LPA on cultured human prostatic SMC from specimens obtained at trans-urethral resection of the prostate (TURP) because of BPH, was analyzed by [3H]-thymidine and [35S]-methionine incorporation. In addition, LPA stimulated BPH SMC were treated with papaverin, forskolin, sildenafil or zaprinast, well known to increase the intracellular level of cAMP or cGMP.

    Results LPA produced a dose-dependent increase in BPH SMC, both regarding DNA- and protein-synthesis with EC50 values of 3 and 10 μM, respectively. Furthermore, both papaverin, a general phosphodiesterase inhibitor regarding cAMP hydrolyzes, and forskolin, an adenylyl cyclase stimulating agent, inhibited the LPA-stimulated DNA replication in a dose dependent manner with IC50  = 2.5, and 0.35 μM, respectively. cGMP increasing agents, such as the NO-donors SIN-1 and SNAP, produced a weak anti-proliferative response. However, both phosphodiesterase 5 inhibitors sildenafil (Viagra®) and zaprinast efficiently blocked DNA replication. In addition, when the protein synthesis was examined, we found that the LPA response was significantly inhibited by forskolin and papaverin.

    Conclusions The major conclusion of this investigation is that the endogenous serum component LPA, is able to promote human BPH SMC growth. In addition, our study indicates that cyclic nucleotides can inhibit this effect. Future clinical studies will be needed to determine if different specific phosphodiesterase inhibitors per se or in combination could represent a new therapeutic possibility for the treatment of BPH.

    Emneord
    BPH, SMC, hyperplastic, PDE, AC, cAMP, cGMP, [H-3]-thymidine, [S-35]-methionine, proliferation
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-47887 (URN)10.1002/pros.10077 (DOI)
    Merknad
    On the day of the defence day the status of this article was submitted.Tilgjengelig fra: 2009-10-11 Laget: 2009-10-11 Sist oppdatert: 2017-12-13bibliografisk kontrollert
    4. Characterization of EDG receptor expression and proliferative response in cultured human BPH smooth muscle cells
    Åpne denne publikasjonen i ny fane eller vindu >>Characterization of EDG receptor expression and proliferative response in cultured human BPH smooth muscle cells
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The endogenous phospholipids, lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are both known to generate a Vvide variety of effects in various cell systems by the endothelial differentiation gene (Edg) receptor family, including 7 different G-protein coupled Edg receptors.

    In this study, expression of LPA- and SlP Edg receptors was examined, and so was the effect with respect to proliferation on cultured BPH smooth muscle cells smc. Mmeover, theresponse on cAMP levels was examined. Finally, a potential link between activation of the MAP kinase cascade and the LPA stimulated proliferation was investigated.

    First, the RT-PCR analysis of the Edg receptors in BPH smc, demonstrated a heterogeneous expression including all receptors except the Edg6 subtype. Further, in contrast to LPA, the mitogen effect of SIP, demonstrated a concentration-dependent biphasic response, including stimulation below 1μM, whereas inhibition was obtained at higher concentrations. Forskolin induced a rapid and transient cAMP response in LPA stimulated cells, with a peak-value after 3 minutes. After 15 minutes the cAMP level had retmned to base-line level. However a gradual increase to 15% of maximum value was obtained after additional 30 minutes, and thereafter a gradual reduction was observed. The mentioned antiproliferative response generated by SIP could not be conelated to an intracellular cAMP increase. Finally, when the LPA treated smc was co-incubated with the MAPK kinase inhibitor PD98059 (10 μM) the mitogen response was eliminated.

    The cAIVIP increase, which was induced by forskolin, corresponds with mentioned antiproliferative effect whereas a similar con-elation was not obtained regarding SIP. The intracellular signal mechanisms triggered by LPA and S1P in BPH smc remain to be further investigated.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-80084 (URN)
    Tilgjengelig fra: 2012-08-20 Laget: 2012-08-20 Sist oppdatert: 2012-08-20bibliografisk kontrollert
  • 208.
    Adolfsson, Per
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Ahlstrand, Christer
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Urologi. Linköpings universitet, Hälsouniversitetet.
    Varenhorst, Eberhard
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Urologi. Linköpings universitet, Hälsouniversitetet.
    Svensson, Samuel
    Linköpings universitet, Institutionen för medicin och hälsa, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Lysophosphatidic acid stimulates proliferation of cultured smooth muscle cells from human BPH tissue: Sildenafil and papaverin generate inhibition2002Inngår i: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 51, nr 1, s. 50-58Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background The endogenous substance lysophosphatidic acid (LPA) has been found to generate proliferation of cultured smooth muscle cells (SMC). Therefore, the effect of LPA on human benign prostate hyperplasia (BPH) could be of interest.

    Methods The proliferative effect of LPA on cultured human prostatic SMC from specimens obtained at trans-urethral resection of the prostate (TURP) because of BPH, was analyzed by [3H]-thymidine and [35S]-methionine incorporation. In addition, LPA stimulated BPH SMC were treated with papaverin, forskolin, sildenafil or zaprinast, well known to increase the intracellular level of cAMP or cGMP.

    Results LPA produced a dose-dependent increase in BPH SMC, both regarding DNA- and protein-synthesis with EC50 values of 3 and 10 μM, respectively. Furthermore, both papaverin, a general phosphodiesterase inhibitor regarding cAMP hydrolyzes, and forskolin, an adenylyl cyclase stimulating agent, inhibited the LPA-stimulated DNA replication in a dose dependent manner with IC50  = 2.5, and 0.35 μM, respectively. cGMP increasing agents, such as the NO-donors SIN-1 and SNAP, produced a weak anti-proliferative response. However, both phosphodiesterase 5 inhibitors sildenafil (Viagra®) and zaprinast efficiently blocked DNA replication. In addition, when the protein synthesis was examined, we found that the LPA response was significantly inhibited by forskolin and papaverin.

    Conclusions The major conclusion of this investigation is that the endogenous serum component LPA, is able to promote human BPH SMC growth. In addition, our study indicates that cyclic nucleotides can inhibit this effect. Future clinical studies will be needed to determine if different specific phosphodiesterase inhibitors per se or in combination could represent a new therapeutic possibility for the treatment of BPH.

  • 209.
    Adolfsson, Per
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Haug, Ingrid
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Berg, Göran
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Svensson, Samuel
    Linköpings universitet, Institutionen för medicin och vård, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Changes in β2-adrenoceptor expression and in adenylyl cyclase and phosphodiesterase activity in human uterine leiomyomas2000Inngår i: Molecular human reproduction, ISSN 1360-9947, E-ISSN 1460-2407, Vol. 6, nr 9, s. 835-842Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Uterine leiomyoma is a very common benign tumour with unclear pathophysiology in adult women. In the present study we have investigated the expression level of α2- and β2-adrenoceptors, and the adenylyl cyclase and phosphodiesterase activity in leiomyoma tissue compared with adjacent myometrium. Our results show that the α22-adrenoceptor ratio is increased in leiomyoma, due to a significant decrease in β2-adrenoceptor expression. These changes were not due to an increased innervation, as the tumour tissue was completely devoid of nerve fibres. Moreover, the adenylyl cyclase activity of leiomyoma membranes was found to be ~50% lower, whereas the phosphodiesterase activity was significantly increased (by ~100%). We found that stimulating an increase in intracellular cyclic AMP, by adenylyl cyclase activity through β2-adrenoceptors (isoprenaline), by direct enzyme activation (forskolin), or by inhibition of phosphodiesterase activity (papaverine), potently blocked both protein and DNA synthesis in cultured leiomyoma smooth muscle cells. Our results imply the adrenoceptors might be involved in, or a consequence of, leiomyoma growth. The results also suggest a new interesting approach for leiomyoma pharmacotherapy.

  • 210.
    Adolfsson, Per I.
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Ahlstrand, Christer
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Urologi. Linköpings universitet, Hälsouniversitetet.
    Varenhorst, Eberhard
    Linköpings universitet, Institutionen för biomedicin och kirurgi, Urologi. Linköpings universitet, Hälsouniversitetet.
    Hultgren, Sitti
    Linköpings universitet, Institutionen för medicin och vård, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Svensson, Samuel P. S.
    Linköpings universitet, Institutionen för medicin och vård, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Characterization of EDG receptor expression and proliferative response in cultured human BPH smooth muscle cellsManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    The endogenous phospholipids, lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are both known to generate a Vvide variety of effects in various cell systems by the endothelial differentiation gene (Edg) receptor family, including 7 different G-protein coupled Edg receptors.

    In this study, expression of LPA- and SlP Edg receptors was examined, and so was the effect with respect to proliferation on cultured BPH smooth muscle cells smc. Mmeover, theresponse on cAMP levels was examined. Finally, a potential link between activation of the MAP kinase cascade and the LPA stimulated proliferation was investigated.

    First, the RT-PCR analysis of the Edg receptors in BPH smc, demonstrated a heterogeneous expression including all receptors except the Edg6 subtype. Further, in contrast to LPA, the mitogen effect of SIP, demonstrated a concentration-dependent biphasic response, including stimulation below 1μM, whereas inhibition was obtained at higher concentrations. Forskolin induced a rapid and transient cAMP response in LPA stimulated cells, with a peak-value after 3 minutes. After 15 minutes the cAMP level had retmned to base-line level. However a gradual increase to 15% of maximum value was obtained after additional 30 minutes, and thereafter a gradual reduction was observed. The mentioned antiproliferative response generated by SIP could not be conelated to an intracellular cAMP increase. Finally, when the LPA treated smc was co-incubated with the MAPK kinase inhibitor PD98059 (10 μM) the mitogen response was eliminated.

    The cAIVIP increase, which was induced by forskolin, corresponds with mentioned antiproliferative effect whereas a similar con-elation was not obtained regarding SIP. The intracellular signal mechanisms triggered by LPA and S1P in BPH smc remain to be further investigated.

  • 211.
    Adolfsson, Per I
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Hälsouniversitetet.
    Bloth, Björn
    Department of Clinical Neuroscience, Laboratory of Translational Neuropharmacology, Center of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
    Hägg, Staffan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Region Östergötland, Diagnostikcentrum, Klinisk farmakologi. Linköpings universitet, Hälsouniversitetet. Futurum Academy for Health and Care, Jönköping County Council, Sweden.
    Svensson, Samuel P S
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Hälsouniversitetet.
    Zinc Induces a Bell-shaped Proliferative Dose-response Effect in Cultured Smooth Muscle Cells From Benign Prostatic Hyperplasia.2015Inngår i: Urology, ISSN 0090-4295, E-ISSN 1527-9995, Vol. 85, nr 3, s. 704.e15-704.e19Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To investigate the effects of zinc (Zn(2+)) concentrations on cultured benign prostatic hyperplasia (BPH) smooth muscle cell (SMC) proliferation.

    METHODS: The effects of Zn(2+) were studied in primary cultures of human BPH SMC, stimulated with either 10-μM lysophosphatidic acid (LPA) or LPA in combination with 100-nM testosterone. Deoxyribonucleic acid replication and protein synthesis using [(3)H]-thymidine and [(35)S]-methionine incorporation were measured. Furthermore, studies were performed to evaluate if Zn(2+) could potentiate the inhibitory effect of phosphodiesterase-5 blockers, on BPH SMC proliferation.

    RESULTS: Zn(2+) generated a bell-shaped concentration response, both regarding deoxyribonucleic acid replication and protein synthesis in cultured BPH SMC. Below a threshold value (approximately 200 μM), a significant mitogenic effect was seen, whereas higher concentrations inhibited SMC proliferation after stimulation with LPA. This effect was even more pronounced after stimulation of LPA in combination with testosterone. Moreover, phosphodiesterase-5 inhibitors, that is, sildenafil blocked LPA-stimulated BPH SMC proliferation. This antiproliferative effect, was significantly potentiated by coincubation with Zn(2+) in an additative manner.

    CONCLUSION: The bell-shaped concentration response of Zn(2+) on cultured BPH SMC proliferation suggests that changes in prostate Zn(2+) concentrations, during aging, diet, or inflammatory conditions, may be of importance in the pathogenesis of BPH.

  • 212.
    Adolfsson, Per I.
    et al.
    Linköpings universitet, Institutionen för medicin och vård, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Dahle, Lars Olav
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Berg, Göran
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet.
    Svensson, Samuel P. S.
    Linköpings universitet, Institutionen för medicin och vård, Farmakologi. Linköpings universitet, Hälsouniversitetet.
    Characterization of α2-Adrenoceptor Subtypes in Pregnant Human Myometrium1998Inngår i: Gynecologic and Obstetric Investigation, ISSN 0378-7346, E-ISSN 1423-002X, Vol. 45, nr 3, s. 145-150Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aim of the present investigation was to determine which subtypes of the α2-adrenoceptors are being expressed in the human pregnant myometrium at term pregnancy. In radioligand binding studies, the specific binding of [3H]rauwolscine to human myometrial membranes was specific and of high affinity with Kd of 2.8 ± 0.6 nM and Bmax of 95 ± 5 fmol/mg protein. Results from competition for the binding of [3H]rauwolscine using subtype-selective ligands, oxymetazoline (α2A-subptype), chlorpromazine (α2B-subtype) and prazosin (α2B-α2C-subtype), suggested that the α2A- and α2B-subtypes are being co-expressed. In order to examine if also the α2C-subtype is being expressed we used an optimal concentration of oxymetazoline or chlorpromazine which would block the high-affinity site, equivalent to the α2A- and α2B-subtype respectively. Competition curves of both oxymetazoline and chlorpromazine still showed a significantly better fit using a two-site model, suggesting that the α2C-subtype also is being expressed. The expression of α2C-subtype mRNA was confirmed using reverse transcription-polymerase chain reaction on mRNA isolated from myometrial biopsies.

    In conclusion, our results suggest that all three subtypes of α2-adrenoceptors are being coexpressed in the human myometrium at term pregnancy and that α2-expression is dominated by the α2A-subtype.

  • 213.
    Adua, Eric
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Oteng Danso, Frank
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Mensah Boa-Amponsem, Oswald
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Medicinska fakulteten.
    Adusei-Mensah, Frank
    University of Cape Coast, Ghana.
    Effect of Neutrophils on Nitric Oxide Production from Stimulated Macrophages2015Inngår i: Iranian Journal of Immunology, ISSN 1735-1383, E-ISSN 1735-367X, Vol. 12, nr 2, s. 94-103Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: During the initial phase of an infection, there is an upregulation of inducible nitric oxide synthase in the macrophages for the production of nitric oxide. This is followed by the recruitment of polymorphonuclear leukocytes (neutrophils) which release arginase. Arginase competes with inducible nitric oxide synthase for a common substrate L-arginine. Objective: To investigate whether the entry of neutrophils and release of arginase can interfere with nitric oxide production from stimulated mouse macrophages. Methods: Neutrophils were isolated from human blood and stimulated with cytodex-3 beads. Cultured macrophages were stimulated with lipopolysaccharide and interferon gamma with or without N (G)-nitro-L-arginine methyl ester or N (omega)-hydroxy-nor-L-arginine. Measurement of NO2-/NO3- and urea were done using the spectrophotometer. Results: A significantly higher level of nitric oxide production from stimulated macrophages was observed compared to control. There was a decrease in nitric oxide production when stimulated macrophages were treated with the supernatant from activated neutrophils (pless than0.05). Conclusion: Arginase from neutrophils can modulate nitric oxide production from activated macrophages which may affect the course of infection by intracellular bacteria.

    Fulltekst (pdf)
    fulltext
  • 214.
    Aerts, Joel
    et al.
    University of Liege, Belgium; University of Paris 07, France.
    Ballinger, James R.
    Guy's and St Thomas' Hospital, London, UK.
    Behe, Martin
    ETH PSI USZ Paul Scherrer Institute, Villigen-PSI, Switzerland.
    Decristoforo, Clemens
    Innsbruck Medical University, Austria.
    Elsinga, Philip H.
    University of Groningen, Netherlands.
    Faivre-Chauvet, Alain
    CHU Nantes, France.
    Mindt, Thomas L.
    University Hospital Basel, Switzerland.
    Kolenc Peitl, Petra
    University Medical Centre Ljubljana, Slovenia.
    Todde, Sergio C.
    University of Milano-Bicocca, Italy.
    Koziorowski, Jacek
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US.
    Guidance on current good radiopharmacy practice for the small-scale preparation of radiopharmaceuticals using automated modules: a European perspective2014Inngår i: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 57, nr 10, s. 615-620Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This document is meant to complement Part B of the EANM Guidelines on current good radiopharmacy practice (cGRPP) in the preparation of radiopharmaceuticals issued by the Radiopharmacy Committee of the European Association of Nuclear Medicine, covering small-scale in-house preparation of radiopharmaceuticals with automated modules. The aim is to provide more detailed and practice-oriented guidance to those who are involved in the small-scale preparation of radiopharmaceuticals, which are not intended for commercial purposes or distribution.

  • 215.
    Aerts, Marc
    et al.
    Interuniversity Institute for Biostatistics and Statistical Bioinformatics.
    Minalu, Girma
    Interuniversity Institute for Biostatistics and Statistical Bioinformatics.
    Bösner, Stefan
    Department of General Practice and Family Medicine, Philipps University Marburg, Germany..
    Buntinx, Frank
    Department of Public Health and Primary Care, KU Leuven, Belgium; Department of General Practice, Maastricht University, The Netherlands..
    Burnand, Bernard
    Institute of Social and Preventive Medicine, Lausanne University Hospital, Switzerland..
    Haasenritter, Jörg
    Department of General Practice and Family Medicine, Philipps University Marburg, Germany..
    Herzig, Lilli
    Institute of Family Medicine, University of Lausanne, Switzerland..
    Knottnerus, J André
    Department of General Practice, Maastricht University, The Netherlands..
    Nilsson, Staffan
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Primärvårdscentrum, Vårdcentralen Vikbolandet.
    Renier, Walter
    Department of Public Health and Primary Care, KU Leuven, Belgium.
    Sox, Carol
    Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, USA..
    Sox, Harold
    Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH , USA; Patient-Centered Outcomes Research Institute, Washington, USA..
    Donner-Banzhoff, Norbert
    Department of General Practice and Family Medicine, Philipps University Marburg, Germany..
    Pooled individual patient data from five countries were used to derive a clinical prediction rule for coronary artery disease in primary care.2017Inngår i: Journal of Clinical Epidemiology, ISSN 0895-4356, E-ISSN 1878-5921, Vol. 81, s. 120-128Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    OBJECTIVE: To construct a clinical prediction rule for coronary artery disease (CAD) presenting with chest pain in primary care.

    STUDY DESIGN AND SETTING: Meta-Analysis using 3,099 patients from five studies. To identify candidate predictors, we used random forest trees, multiple imputation of missing values, and logistic regression within individual studies. To generate a prediction rule on the pooled data, we applied a regression model that took account of the differing standard data sets collected by the five studies.

    RESULTS: The most parsimonious rule included six equally weighted predictors: age ≥55 (males) or ≥65 (females) (+1); attending physician suspected a serious diagnosis (+1); history of CAD (+1); pain brought on by exertion (+1); pain feels like "pressure" (+1); pain reproducible by palpation (-1). CAD was considered absent if the prediction score is <2. The area under the ROC curve was 0.84. We applied this rule to a study setting with a CAD prevalence of 13.2% using a prediction score cutoff of <2 (i.e., -1, 0, or +1). When the score was <2, the probability of CAD was 2.1% (95% CI: 1.1-3.9%); when the score was ≥ 2, it was 43.0% (95% CI: 35.8-50.4%).

    CONCLUSIONS: Clinical prediction rules are a key strategy for individualizing care. Large data sets based on electronic health records from diverse sites create opportunities for improving their internal and external validity. Our patient-level meta-analysis from five primary care sites should improve external validity. Our strategy for addressing site-to-site systematic variation in missing data should improve internal validity. Using principles derived from decision theory, we also discuss the problem of setting the cutoff prediction score for taking action.

    Fulltekst (pdf)
    fulltext
  • 216.
    Aesoy, R.
    et al.
    Department of Oncology/Pathology, Karolinska Biomics Center, Karolinska Institutet, Stockholm, Sweden.
    Sanchez, B.C.
    Department of Oncology/Pathology, Karolinska Biomics Center, Karolinska Institutet, Stockholm, Sweden.
    Norum, J.H.
    Department of Pharmacology, University of Oslo, Oslo, Norway.
    Lewensohn, R.
    Department of Oncology/Pathology, Karolinska Biomics Center, Karolinska Institutet, Stockholm, Sweden.
    Viktorsson, K.
    Department of Oncology/Pathology, Karolinska Biomics Center, Karolinska Institutet, Stockholm, Sweden.
    Linderholm, Barbro
    Östergötlands Läns Landsting, Kirurgi- och onkologicentrum, Onkologiska kliniken US.
    An autocrine VEGF/VEGFR2 and p38 signaling loop confers resistance to 4-hydroxytamoxifen in MCF-7 breast cancer cells2008Inngår i: Molecular Cancer Research, ISSN 1541-7786, E-ISSN 1557-3125, Vol. 6, nr 10, s. 1630-1638Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Tamoxifen, a partial estrogen receptor antagonist, is part of the standard treatment of both primary and advanced breast cancers. However, significant proportions of breast cancers are either de novo resistant or develop tamoxifen resistance during the course of treatment through mechanisms which have been only partly characterized. We have previously found that high vascular endothelial growth factor (VEGF) or VEGF receptor 2 (VEGFR2) expression and concomitant high p38 mitogen-activated protein kinase activity within breast cancers predict a poor outcome for tamoxifen-treated patients. Here, we have molecularly dissected how VEGF/VEGFR2 and p38 are linked, and contribute to tamoxifen resistance within breast cancer using a MCF-7 BC cell model with different 4-hydroxytamoxifen (4-OHT) responsiveness. We report that MCF-7 breast cancer cell lines with tamoxifen resistance have increased secretion of VEGF and increased signaling through VEGFR2 compared with parental MCF-7 cells. 4-OHT treatment caused the ablation of VEGF secretion in parental MCF-7 cells, whereas in the tamoxifen-resistant subline, a VEGF/ VEGFR2 signaling loop was still evident upon treatment. Increased basal levels of total and phosphorylated p38 were observed in tamoxifen-resistant cells. Pharmacologic inhibition of p38 reduced the proliferation of both tamoxifen-responsive and tamoxifen-resistant cells and showed an additive growth-inhibitory effect in combination with 4-OHT. A connection between VEGF/ VEGFR2 and p38 signaling was identified by VEGF and VEGFR2 knockdown, which equally reduced both the total and the active forms of p38 in tamoxifen-resistant cells. Taken together, our results suggest that decreased sensitivityto 4-OHT is caused by a death-protecting VEGF/VEGFR2 and p38 growth factor loop in breast cancer cells. Inhibition of these signaling pathways may be beneficial to overcome tamoxifen resistance. Copyright © 2008 American Association for Cancer Research.

  • 217.
    af Klercker, Tom
    Linköpings universitet, Institutionen för hälsa och samhälle, Allmänmedicin. Linköpings universitet, Hälsouniversitetet.
    Method for inductive case-based decision support system over the Internet: exemplified by ear, nose and throat diagnostics in primary care1997Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis is an example of an ear to loaf process:

    A Preliminary Essential Data Set (PEDS) for Ear, Nose and Throat (ENT) diagnostics in Primary Health Care (PHC) was established by infologic modelling of existing tractates, between the specialist organisations of ENT and PHC, and four contemporary text-books on the subject (I). The PEDS was then compared to the aggregated data from a sample of case-files from a Swedish PHC centre. The quality of the individual medical record was found to be poor and not sufficient for follow-up and Quality Management (QM) purposes (II). The aggregated data from the case-file sample was processed by an inductive "expert" computer program that generated a decision-tree, based on the total number of decisions (diagnoses) in the data-base. This was nearly identical to the PEDS and somewhat less complicated. Infological modelling of the PEDS and the decision-tree resulted in the proposed Essential Data Set (EDS) for ENT diagnostics in PHC. The decision tree was "pruned" to achieve simplicity and ease of use (III). It was converted into a Computer-aided Decision Support System (CDSS) and put on the Internet using World Wide Web (WWW) tools (IV). This system was then implemented in the Skänninge PHC centre where an Electronic Medical Record System (EMRS) was in everyday use. Due to technical difficulties no integration between the two systems was possible. The CDSS was run on a computer outside the centre and this raised the question of secrecy and security (V). Prior to the implementation, and after a study period of four months attitudes towards, and the acceptance of, new Information Technology (IT) was explored by using focus group methodology (VI). It is important that those who are to use the system are intimately involved in its development. The results showed, that participation of the end-users during implementation is crucial for its acceptance. The need for a uniform and agreed terminology was obvious to facilitate co-operation and QM. The importance of nurses and physicians using the same terminology for documentation, was paramount.

  • 218.
    Af Sandeberg, Margareta
    et al.
    Astrid Lindgrens Childrens Hospital.
    Gustafsson, Karin
    Queen Silvias Childrens Hospital.
    Olsson, Maria
    Queen Silvias Childrens Hospital.
    Renstrom, Maria
    Umea University Hospital.
    Sandgren, Marie
    Östergötlands Läns Landsting.
    Turup, Eva
    Akad Childrens Hospital.
    Mahl, Carina
    Lund Undivers Hospital.
    THE PROCESS IN FORMING NATIONAL RECOMMENDATIONS FOR SOCIAL LIFE AMONG CHILDREN UNDERGOING CANCER TREATMENT in PEDIATRIC BLOOD and CANCER, vol 55, issue 5, pp 980-9812010Inngår i: PEDIATRIC BLOOD and CANCER, John Wiley andamp;amp; Sons, Ltd , 2010, Vol. 55, nr 5, s. 980-981Konferansepaper (Fagfellevurdert)
    Abstract [en]

    n/a

  • 219.
    Af Sandeberg, Margareta
    et al.
    Department of Women's and Children's Health, Karolinska Institutet, Children's and Women's Health, Karolinska University Hospital.
    Wenemark, Marika
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för verksamhetsstöd och utveckling, Verksamhetsutveckling vård och hälsa.
    Bartholdson, Cecilia
    Department of Women's and Children's Health, Karolinska Institutet, Children's and Women's Health, Karolinska University Hospital.
    Lützén, Kim
    Department of Women's and Children's Health, Karolinska Institutet.
    Pergert, Pernilla
    Department of Women's and Children's Health, Karolinska Institutet, Children's and Women's Health, Karolinska University Hospital.
    To change or not to change - translating and culturally adapting the paediatric version of the Moral Distress Scale-Revised (MDS-R)2017Inngår i: BMC Medical Ethics, ISSN 1472-6939, E-ISSN 1472-6939, Vol. 18, nr 14, s. 1-9Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Paediatric cancer care poses ethically difficult situations that can lead to value conflicts about what is best for the child, possibly resulting in moral distress. Research on moral distress is lacking in paediatric cancer care in Sweden and most questionnaires are developed in English. The Moral Distress Scale-Revised (MDS-R) is a questionnaire that measures moral distress in specific situations; respondents are asked to indicate both the frequency and the level of disturbance when the situation arises. The aims of this study were to translate and culturally adapt the questionnaire to the context of Swedish paediatric cancer care. In doing so we endeavoured to keep the content in the Swedish version as equivalent to the original as possible but to introduce modifications that improve the functional level and increase respondent satisfaction.

    METHODS: The procedure included linguistic translation and cultural adaptation of MDS-R's paediatric versions for Physicians, Nurses and Other Healthcare Providers to the context of Swedish paediatric cancer care. The process of adjustment included: preparation, translation procedure and respondent validation. The latter included focus group and cognitive interviews with healthcare professionals in paediatric cancer care.

    RESULTS: To achieve a Swedish version with a good functional level and high trustworthiness, some adjustments were made concerning design, language, cultural matters and content. Cognitive interviews revealed problems with stating the level of disturbance hypothetically and items with negations caused even more problems, after having stated that the situation never happens.

    CONCLUSIONS: Translation and cultural adaptation require the involvement of various types of specialist. It is difficult to combine the intention to keep the content as equivalent to the original as possible with the need for modifications that improve the functional level and increase respondent satisfaction. The translated and culturally adapted Swedish MDS-R seems to have equivalent content as well as improved functional level and respondent satisfaction. The adjustments were made to fit paediatric cancer care but it could be argued that the changes are relevant for most areas of paediatric care of seriously ill patients.

    Fulltekst (pdf)
    To change or not to change - translating and culturally adapting the paediatric version of the Moral Distress Scale-Revised (MDS-R)
  • 220.
    Afoke, Anthony Okoro
    Linköpings universitet, Institutionen för molekylär och klinisk medicin, Pediatrik. Linköpings universitet, Hälsouniversitetet.
    Some epidemiological aspects of insulin-dependent diabetes mellitus in Nigeria and Sweden1993Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    In the western world diabetes mellitus is one of the most common severe diseases in childhood, but it is rarely seen in black African populations. However, there are very few epidemiological studies of childhood diabetes in Africa and almost nothing is known of the Nigerian population. One aim of this study was therefore to estimate the prevalence of insulin dependent diabetes (IDDM) in children and adolescents and to characterize their type of diabetes.

    A screening of almost 78,000 school children was performed and beside some already known diabetic patients several new cases were diagnosed. It was found that IDDM is much less common than in Europe but on the other hand more common than in several Asian countries. In addition the prevalence found may be underestimated because of cultural and social factors, health care problems and high mortality in diabetes. Although most patients had a clinical picture of Malnutrition Related Diabetes (MRD) we found in some cases autoantibodies towards islet cells and insulin and furthermore the same HLA-DQ-type-associations as seen to Type 1 diabetes in caucasian diabetics.

    While we saw no seasonal variation of diagnosis of Nigerian IDDM, there is a pronounced such seasonal variation in Sweden. This study has tried to elucidate whether this seasonal variation is related to any differences in manifestation and clinical course. Patients diagnosed during incidence peaks had more often short duration of symptoms before diagnosis,ketonuria at diagnosis, rapid loss of endogenous insulin secretion but increase of insulin antibodies and of glycosylated haemoglobin. They had also more often infections before diagnosis and high serum immunoglobulins (IgG and IgM) up to 9 months after diagnosis. HLA-DR4 was more common in these patients. The results suggest that IDDM in Swedish children is heterogenous.

  • 221. Bestill onlineKjøp publikasjonen >>
    Afrell, Maria
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Hälsouniversitetet.
    Att leva med en kropp som värker: samtal med fysioterapeuten2014Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background and aim: Physiotherapists in primary care meet, assess and treat patients with long-standing benign musculoskeletal pain. As a clinical condition, long-standing pain is common but nonetheless it is quite complex. The aim of this thesis has been, from a bodily existential perspective, to investigate and conceptualise the experience of living with longstanding benign musculoskeletal pain, and from there, to work out a method for conversation and assessment within non-specialised physiotherapy.

    Methods: Our first study was an interview study where we applied a phenomenological approach and investigated the ways individuals suffering from long-standing pain experienced their body and their illness. Four aspects of body experience were described, and based on these aspects, four typologies of attitudes to pain were distinguished. In the second study, we made two group interviews with six physiotherapists about their experiences of using, in their clinical work, questions from the interview guide in study I that had given particularly rich responses. Transcripts were analysed using phenomenography. In the third study, patients’ verbal responses to the key questions, directed to them by physiotherapists in clinical situations, were investigated, and the four aspects of body experience from study I formed the concepts of a deductive analysis. In study IV, finally, the key questions and typologies were tried by a larger group (31), and their experiences and the possible applicability of the method were studied by qualitative content analysis combined with the counting of codes.

    Results: We created four typologies of attitudes to long-standing pain: “Surrendering to one’s fate”, “Accepting by an active process of change”, “Balancing between hope and resignation” and “Rejecting the body”. These typologies, in turn, were based on four aspects of body experience: “The body as an aspect of identity”. “Body reliance”, “Body awareness”, and “Ways of understanding pain”. In study II, by the aid of key questions,  patient and physiotherapist managed to have a conversation on bodily existential matters. The physiotherapist learnt to know the patient as a person, a process appeared to be initiated in the patient, and their relation changed. The patient was willing to talk about her body in pain, and had the words to do this. In study III, the key questions opened ways to reflections on body, existence, and biography. The four aspects of body experience were central to the patients’ descriptions. In study IV, the participating physiotherapists reported by large positive experiences from applying key questions and typologies. The patients reflected, emotions were evoked, and the relation and the communication often improved. The typologies helped in giving a comprehensive perspective of the patient’s problem, and to grasp where in the process of rehabilitation the patient was to be found.

    Conclusions: The method, seven key questions combined with the tentative frame of interpretation of the answers, seemed to be easily applied by interested physiotherapists in non-specialised practice. The application of the method addresses the need of developing the professional role of the physiotherapist. The challenge is to face the whole person, who is her lived body as well as her identity crisis, carried by emotions such as grief and anger. This may inspire the use of the full potential of the physiotherapist’s professional role in the clinical encounter.

    Delarbeid
    1. Living with a body in pain – between acceptance and denial
    Åpne denne publikasjonen i ny fane eller vindu >>Living with a body in pain – between acceptance and denial
    2007 (engelsk)Inngår i: Scandinavian Journal of Caring Sciences, ISSN 0283-9318, E-ISSN 1471-6712, Vol. 21, nr 3, s. 291-296Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The aetiology of nonspecific musculoskeletal pain is considered to be multi-factorial. Long-standing pain not only has a negative impact on the individual's general health but also changes the individual's experience of him/her self and his/her world. The aim of this study was to describe how individuals with long-standing musculoskeletal pain, in a bodily existential perspective, relate to their aching body. Semi-structured interviews with 20 patients were analysed using mainly a phenomenological-hermeneutic method. From the analysis, four main categories reflect the meaning contents of the interviews: the body as an aspect of identity; body reliance; body awareness; ways of understanding pain. From these categories, four distinct typologies were inferred: surrendering to ones fate; accepting by an active process of change; balancing between hope and resignation; rejecting the body. The result indicates that patients with long-standing pain are to be found along a spectrum from accepting to rejecting the aching body. Body awareness and body reliance seem to have importance in the process of acceptance of the body as well as life situation as a whole, which we regard as interesting hypotheses for further inquiry.

    sted, utgiver, år, opplag, sider
    John Wiley & Sons, 2007
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-106745 (URN)10.1111/j.1471-6712.2007.00475.x (DOI)17727540 (PubMedID)
    Tilgjengelig fra: 2014-05-21 Laget: 2014-05-21 Sist oppdatert: 2017-12-05bibliografisk kontrollert
    2. We got the whole story all at once: physiotherapists use of key questions when meeting patients with long-standing pain
    Åpne denne publikasjonen i ny fane eller vindu >>We got the whole story all at once: physiotherapists use of key questions when meeting patients with long-standing pain
    2010 (engelsk)Inngår i: SCANDINAVIAN JOURNAL OF CARING SCIENCES, ISSN 0283-9318, Vol. 24, nr 2, s. 281-289Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Long-standing musculoskeletal pain has many dimensions. Physiotherapy lacks a tested method of dialogue with which physiotherapists and patients can together explore pain in all its complexity. The present aim was to find out how physiotherapists experienced the influence of systematically prepared key questioning on their relation to, and understanding of, patients with long-standing pain. A group of six physiotherapists with long experience of pain rehabilitation used such questions in their encounters with their patients. Two periods of work with the questions were followed by discussions in which the physiotherapists shared their experience in a joint focus group. Verbatim transcripts of the discussions constitute the data of the study. A phenomenographic method was used for the analysis. The responses to the key questions gave the physiotherapists an insight into the patient as a person. The questions started a process of change in the patient, and changed the physiotherapists relation to her or him. The patient expressed feelings and experience, and this also seemed to encourage a change in chosen coping strategies. This new content of the interaction challenged the physiotherapists role, thus raising questions about her professional mandate.

    sted, utgiver, år, opplag, sider
    Blackwell Publishing Ltd, 2010
    Emneord
    qualitative method, phenomenography, dialogue method, key questions, biopsychosocial, pain management, physiotherapy, professional mandate
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-56678 (URN)10.1111/j.1471-6712.2009.00718.x (DOI)000277713500011 ()
    Tilgjengelig fra: 2010-05-31 Laget: 2010-05-31 Sist oppdatert: 2014-05-21
    3. Telling about long-lasting pain – the role of key questions in physiotherapy encounters
    Åpne denne publikasjonen i ny fane eller vindu >>Telling about long-lasting pain – the role of key questions in physiotherapy encounters
    2014 (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Aim: For a physiotherapist in primary care wishing to meet her/his patient in the entirety of possible causes of long-lasting pain, the ability to perceive its nuances and context is indispensable.

    The aim was to investigate the verbal responses of patients with long-lasting pain to key questions addressing their biography, identity and lived body.

    Methodology: Three Swedish physiotherapists asked eight patients with long-lasting pain seven questions regarding body experience at the introductory and concluding, tape-recorded, treatment sessions. A deductive, qualitative analysis was made through four concepts naming aspects of body experience: body reliance, body awareness, models for explaining pain and the body’s integration in the identity.

    Major findings: The key questions opened ways to bodily-existential reflections. The aspects of body experience were central to the patients’ descriptions. Appreciable differences emerged between the patients in how they described the experience of living with pain, and in some cases differences were seen between the conversations of the first and the last treatment session with the same patient.

    Conclusions: The questions addressed crucial issues of living with pain and seem to have a potential to capture changes in body experience. Physiotherapists may recognize their patients’ biographical disruptions, reconstruction and adapt their treatment accordingly.

    Emneord
    Pain management, Clinical dialogue, Physiotherapy, Bodily existential perspective, Body awareness, Body reliance, Key questions, Deductive qualitative analysis
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-106746 (URN)
    Tilgjengelig fra: 2014-05-21 Laget: 2014-05-21 Sist oppdatert: 2014-05-21bibliografisk kontrollert
    4. Improving the interaction between the physiotherapist and the patient with long-lasting pain
    Åpne denne publikasjonen i ny fane eller vindu >>Improving the interaction between the physiotherapist and the patient with long-lasting pain
    2014 (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Purpose: To investigate whether it would be possible to improve the understanding and communication between physiotherapists and patients with long-lasting pain by, in a systematic way, approaching their condition from a bodily existential perspective.

    Method: 31 physiotherapists answered written open questions about what happened when they in 90 encounters used key questions about living with pain together with a tentative frame for interpreting the answers - typologies of approaches to living with long-lasting pain. In the analysis, we combined qualitative content analysis with the counting of the numbers of codes.

    Results: According to the physiotherapists, patients were positive to answering the key questions, which also evoked emotional responses and reflection. The relation between the physiotherapists and their patients improved. The typologies helped the physiotherapists understand their patients better, as well as in assessing the patients’ problems and choosing treatment. In all, positive experience clearly dominated. Conclusion: When used by physiotherapists with an interest in patients with longlasting pain, the key questions and typologies seem to enrich the clinical interaction in many cases. To try the generalisability of our findings, we regard it an interesting possibility to conduct a larger, quantitative questionnaire study based on the experiences and results of the present one.

    Emneord
    Qualitative method, pain management, pain assessment, clinical dialogue, communication, bodily existential, physiotherapy
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-106747 (URN)
    Tilgjengelig fra: 2014-05-21 Laget: 2014-05-21 Sist oppdatert: 2014-05-21bibliografisk kontrollert
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    Att leva med en kropp som värker: samtal med fysioterapeuten
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    Bilaga 2
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    Errata
  • 222.
    Afrell, Maria
    et al.
    Unit of Rehabilitation, Kalmer County Council, Västervik.
    Biguet, Gabriele
    Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, Karolinska Institutet, Stockholm.
    Rudebeck, Carl Edvard
    Department of Neurobiology, Care Sciences and Society, Division of Physiotherapy, Karolinska Institutet, Stockholm.
    Living with a body in pain – between acceptance and denial2007Inngår i: Scandinavian Journal of Caring Sciences, ISSN 0283-9318, E-ISSN 1471-6712, Vol. 21, nr 3, s. 291-296Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The aetiology of nonspecific musculoskeletal pain is considered to be multi-factorial. Long-standing pain not only has a negative impact on the individual's general health but also changes the individual's experience of him/her self and his/her world. The aim of this study was to describe how individuals with long-standing musculoskeletal pain, in a bodily existential perspective, relate to their aching body. Semi-structured interviews with 20 patients were analysed using mainly a phenomenological-hermeneutic method. From the analysis, four main categories reflect the meaning contents of the interviews: the body as an aspect of identity; body reliance; body awareness; ways of understanding pain. From these categories, four distinct typologies were inferred: surrendering to ones fate; accepting by an active process of change; balancing between hope and resignation; rejecting the body. The result indicates that patients with long-standing pain are to be found along a spectrum from accepting to rejecting the aching body. Body awareness and body reliance seem to have importance in the process of acceptance of the body as well as life situation as a whole, which we regard as interesting hypotheses for further inquiry.

  • 223.
    Afrell, Maria
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet. Samrehab, Kalmar County Council, Västervik Hospital, Sweden.
    Brudin, Lars
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Hälsouniversitetet. Department of Clinical Physiology, Kalmar County Hospital, Kalmar, Sweden.
    Rudebeck, Carl Edvard
    Department of Community Medicine, University of Tromsö, Norway / The Research Unit, Kalmar County Council, Sweden.
    Improving the interaction between the physiotherapist and the patient with long-lasting pain2014Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Purpose: To investigate whether it would be possible to improve the understanding and communication between physiotherapists and patients with long-lasting pain by, in a systematic way, approaching their condition from a bodily existential perspective.

    Method: 31 physiotherapists answered written open questions about what happened when they in 90 encounters used key questions about living with pain together with a tentative frame for interpreting the answers - typologies of approaches to living with long-lasting pain. In the analysis, we combined qualitative content analysis with the counting of the numbers of codes.

    Results: According to the physiotherapists, patients were positive to answering the key questions, which also evoked emotional responses and reflection. The relation between the physiotherapists and their patients improved. The typologies helped the physiotherapists understand their patients better, as well as in assessing the patients’ problems and choosing treatment. In all, positive experience clearly dominated. Conclusion: When used by physiotherapists with an interest in patients with longlasting pain, the key questions and typologies seem to enrich the clinical interaction in many cases. To try the generalisability of our findings, we regard it an interesting possibility to conduct a larger, quantitative questionnaire study based on the experiences and results of the present one.

  • 224.
    Afrell, Maria
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Hälsouniversitetet. Samrehab, Västerviks sjukhus, Kalmar County Council, Sweden.
    Rudebeck, Carl Edvard
    Department of Community Medicine, Tromsö University, Tromsö, Norway / The Research Unit, Kalmar County Council, Sweden.
    Telling about long-lasting pain – the role of key questions in physiotherapy encounters2014Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Aim: For a physiotherapist in primary care wishing to meet her/his patient in the entirety of possible causes of long-lasting pain, the ability to perceive its nuances and context is indispensable.

    The aim was to investigate the verbal responses of patients with long-lasting pain to key questions addressing their biography, identity and lived body.

    Methodology: Three Swedish physiotherapists asked eight patients with long-lasting pain seven questions regarding body experience at the introductory and concluding, tape-recorded, treatment sessions. A deductive, qualitative analysis was made through four concepts naming aspects of body experience: body reliance, body awareness, models for explaining pain and the body’s integration in the identity.

    Major findings: The key questions opened ways to bodily-existential reflections. The aspects of body experience were central to the patients’ descriptions. Appreciable differences emerged between the patients in how they described the experience of living with pain, and in some cases differences were seen between the conversations of the first and the last treatment session with the same patient.

    Conclusions: The questions addressed crucial issues of living with pain and seem to have a potential to capture changes in body experience. Physiotherapists may recognize their patients’ biographical disruptions, reconstruction and adapt their treatment accordingly.

  • 225.
    Afzelius, Maria
    et al.
    Malmö University, Sweden.
    Ostman, Margareta
    Malmö University, Sweden.
    Råstam, Maria
    Lund University, Sweden; University of Gothenburg, Sweden.
    Priebe, Gisela
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Barnafrid. Linköpings universitet, Medicinska fakulteten. Lund University, Sweden.
    Parents in adult psychiatric care and their children: a call for more interagency collaboration with social services and child and adolescent psychiatry2018Inngår i: Nordic Journal of Psychiatry, ISSN 0803-9488, E-ISSN 1502-4725, Vol. 72, nr 1, s. 31-38Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: A parental mental illness affects all family members and should warrant a need for support.Aim: To investigate the extent to which psychiatric patients with underage children are the recipients of child-focused interventions and involved in interagency collaboration.Methods: Data were retrieved from a psychiatric services medical record database consisting of data regarding 29,972 individuals in southern Sweden and indicating the patients main diagnoses, comorbidity, children below the age of 18, and child-focused interventions.Results: Among the patients surveyed, 12.9% had registered underage children. One-fourth of the patients received child-focused interventions from adult psychiatry, and out of these 30.7% were involved in interagency collaboration as compared to 7.7% without child-focused interventions. Overall, collaboration with child and adolescent psychiatric services was low for all main diagnoses. If a patient received child-focused interventions from psychiatric services, the likelihood of being involved in interagency collaboration was five times greater as compared to patients receiving no child-focused intervention when controlled for gender, main diagnosis, and inpatient care.Conclusions: Psychiatric services play a significant role in identifying the need for and initiating child-focused interventions in families with a parental mental illness, and need to develop and support strategies to enhance interagency collaboration with other welfare services.

  • 226.
    Agalave, Nilesh M
    et al.
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Max
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
    Abdelmoaty, Sally
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Su, Jie
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Baharpoor, Azar
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Lundbäck, Peter
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Palmblad, Karin
    Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Ulf
    Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden.
    Harris, Helena
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden.
    Svensson, Camilla I
    Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
    Spinal HMGB1 induces TLR4-mediated long-lasting hypersensitivity and glial activation and regulates pain-like behavior in experimental arthritis.2014Inngår i: Pain, ISSN 0304-3959, E-ISSN 1872-6623, Vol. 155, nr 9, s. 1802-1813Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Extracellular high mobility group box-1 protein (HMGB1) plays important roles in the pathogenesis of nerve injury- and cancer-induced pain. However, the involvement of spinal HMGB1 in arthritis-induced pain has not been examined previously and is the focus of this study. Immunohistochemistry showed that HMGB1 is expressed in neurons and glial cells in the spinal cord. Subsequent to induction of collagen antibody-induced arthritis (CAIA), Hmgb1 mRNA and extranuclear protein levels were significantly increased in the lumbar spinal cord. Intrathecal (i.t.) injection of a neutralizing anti-HMGB1 monoclonal antibody or recombinant HMGB1 box A peptide (Abox), which each prevent extracellular HMGB1 activities, reversed CAIA-induced mechanical hypersensitivity. This occurred during ongoing joint inflammation as well as during the postinflammatory phase, indicating that spinal HMGB1 has an important function in nociception persisting beyond episodes of joint inflammation. Importantly, only HMGB1 in its partially oxidized isoform (disulfide HMGB1), which activates toll-like receptor 4 (TLR4), but not in its fully reduced or fully oxidized isoforms, evoked mechanical hypersensitivity upon i.t. injection. Interestingly, although both male and female mice developed mechanical hypersensitivity in response to i.t. HMGB1, female mice recovered faster. Furthermore, the pro-nociceptive effect of i.t. injection of HMGB1 persisted in Tlr2- and Rage-, but was absent in Tlr4-deficient mice. The same pattern was observed for HMGB1-induced spinal microglia and astrocyte activation and cytokine induction. These results demonstrate that spinal HMGB1 contributes to nociceptive signal transmission via activation of TLR4 and point to disulfide HMGB1 inhibition as a potential therapeutic strategy in treatment of chronic inflammatory pain.

  • 227.
    Ageberg, Eva
    et al.
    Lund Univ, Sweden.
    Bunke, Sofia
    Lund Univ, Sweden.
    Lucander, Karolina
    Lund Univ, Sweden.
    Nilsen, Per
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten.
    Donaldson, Alex
    La Trobe Univ, Australia; Federat Univ Australia, Australia.
    Facilitators to support the implementation of injury prevention training in youth handball: A concept mapping approach2019Inngår i: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 29, nr 2, s. 275-285Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There is a need for research to identify effective implementation strategies for injury prevention training within real-world community sports. The aim of this ecological participatory study was to identify facilitators, among stakeholders at multiple levels, that could help injury prevention training become part of regular training routines in youth team handball. Concept mapping, a mixed-method approach for qualitative data collection and quantitative data analysis, was used. Stakeholders (n = 196) of two community team handball clubs (29% players, 13% coaches, 38% caregivers, 11% club, district and national handball administrators, 9% unknown) participated in a brainstorming process. After the research team synthesized the 235 generated statements, 50 stakeholders (34% players, 22% coaches, 24% caregivers, 20% administrators) sorted 89 unique facilitator statements into clusters and rated them for importance and feasibility. Multidimensional scaling and hierarchical cluster analysis yielded five clusters (stress value 0.231): "Understanding and applying knowledge," "Education, knowledge, and consistency," "Set-up and exercises," "Inspiration, motivation, and routines," and "Club policy and expert collaboration." The cluster "Understanding and applying knowledge" had the highest mean importance (3.17 out of 4) and feasibility (2.93) ratings. The 32 statements rated as both highly important and feasible (Go-zone) indicate action is required at the individual (end-users) and organizational (policymakers) levels to implement injury prevention training. Results suggest that developing evidence-based context-specific injury prevention training, incorporating physiological, biomechanical and psychological components, and an associated context-specific implementation plan in partnership with all stakeholders should be a high priority to facilitate the implementation of injury prevention training in youth team handball.

    Fulltekst (pdf)
    fulltext
  • 228.
    Ageberg, Eva
    et al.
    Lund Univ, Sweden.
    Bunke, Sofia
    Lund Univ, Sweden.
    Nilsen, Per
    Linköpings universitet, Institutionen för hälsa, medicin och vård, Avdelningen för samhälle och hälsa. Linköpings universitet, Medicinska fakulteten.
    Donaldson, Alex
    La Trobe Univ, Australia.
    Planning injury prevention training for youth handball players: application of the generalisable six-step intervention development process2020Inngår i: Injury Prevention, ISSN 1353-8047, E-ISSN 1475-5785, Vol. 26, nr 2, s. 164-169Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background Youth handball players are vulnerable to injuries. Because there is no available injury prevention training specifically developed for youth handball players targeting both upper and lower limbs or incorporating psychological aspects of injury, we undertook the Implementing injury Prevention training ROutines in TEams and Clubs in youth Team handball (I-PROTECT) project. We used an ecological participatory design incorporating the perspectives of multiple stakeholders (health beneficiaries, programme deliverers and policy makers). The aim of this paper was to describe the process of developing the I-PROTECT model, featuring injury prevention training and an accompanying implementation strategy. Design We used the generalisable six-step intervention development process, outlined to guide researchers when developing implementable, evidence-based sports injury prevention interventions, to develop the I-PROTECT model. The six-step process involves establishing a research-stakeholder collaborative partnership to (1) identify and synthesise research evidence and clinical experience; (2) consult with relevant experts; (3) engage end users to ensure their needs, capacity and values are considered; (4) test the feasibility and acceptability of the intervention; (5) evaluate the intervention against theory; and (6) obtain feedback from early implementers. Two community handball clubs in southern Sweden, offering organised training for youth male and female players, and the district handball federation, participate in the intervention development. Drafts of the I-PROTECT model will be developed and revised with key stakeholder advice and input throughout all six steps. Conclusion The I-PROTECT model described will be an end user-driven intervention, including evidence-based, theory-informed and context-specific injury prevention training for youth handball, and an associated implementation strategy.

    Fulltekst (pdf)
    fulltext
  • 229.
    Agebratt, Christian
    et al.
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten.
    Ström, Edvin
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten.
    Romu, Thobias
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
    Dahlqvist Leinhard, Olof
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för radiologiska vetenskaper. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Centrum för kirurgi, ortopedi och cancervård, Radiofysikavdelningen US.
    Borga, Magnus
    Linköpings universitet, Centrum för medicinsk bildvetenskap och visualisering, CMIV. Linköpings universitet, Institutionen för medicinsk teknik. Linköpings universitet, Tekniska fakulteten.
    Leandersson, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Arbets- och miljömedicin.
    Nyström, Fredrik H.
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    A Randomized Study of the Effects of Additional Fruit and Nuts Consumption on Hepatic Fat Content, Cardiovascular Risk Factors and Basal Metabolic Rate2016Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 1, s. e0147149-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background

    Fruit has since long been advocated as a healthy source of many nutrients, however, the high content of sugars in fruit might be a concern.

    Objectives

    To study effects of an increased fruit intake compared with similar amount of extra calories from nuts in humans.

    Methods

    Thirty healthy non-obese participants were randomized to either supplement the diet with fruits or nuts, each at +7 kcal/kg bodyweight/day for two months. Major endpoints were change of hepatic fat content (HFC, by magnetic resonance imaging, MRI), basal metabolic rate (BMR, with indirect calorimetry) and cardiovascular risk markers.

    Results

    Weight gain was numerically similar in both groups although only statistically significant in the group randomized to nuts (fruit: from 22.15±1.61 kg/m2 to 22.30±1.7 kg/m2, p = 0.24 nuts: from 22.54±2.26 kg/m2 to 22.73±2.28 kg/m2, p = 0.045). On the other hand BMR increased in the nut group only (p = 0.028). Only the nut group reported a net increase of calories (from 2519±721 kcal/day to 2763±595 kcal/day, p = 0.035) according to 3-day food registrations. Despite an almost three-fold reported increased fructose-intake in the fruit group (from 9.1±6.0 gram/day to 25.6±9.6 gram/day, p<0.0001, nuts: from 12.4±5.7 gram/day to 6.5±5.3 gram/day, p = 0.007) there was no change of HFC. The numerical increase in fasting insulin was statistical significant only in the fruit group (from 7.73±3.1 pmol/l to 8.81±2.9 pmol/l, p = 0.018, nuts: from 7.29±2.9 pmol/l to 8.62±3.0 pmol/l, p = 0.14). Levels of vitamin C increased in both groups while α-tocopherol/cholesterol-ratio increased only in the fruit group.

    Conclusions

    Although BMR increased in the nut-group only this was not linked with differences in weight gain between groups which potentially could be explained by the lack of reported net caloric increase in the fruit group. In healthy non-obese individuals an increased fruit intake seems safe from cardiovascular risk perspective, including measurement of HFC by MRI.

    Fulltekst (pdf)
    fulltext
  • 230.
    Ageno, Walter
    et al.
    University of Insubria, Italy.
    Buller, Harry R.
    Academic Medical Centre, Netherlands.
    Falanga, Anna
    Hospital Papa Giovanni XXIII, Italy; Hospital Papa Giovanni XXIII, Italy.
    Hacke, Werner
    Heidelberg University, Germany.
    Hendriks, Jeroen
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för omvårdnad. Linköpings universitet, Medicinska fakulteten. University of Adelaide, Australia.
    Lobban, Trudie
    Arrhythmia Alliance and AF Assoc, England.
    Merino, Jose
    University of La Paz, Spain.
    Milojevic, Ivan S.
    Gen Hospital Cuprija, Serbia.
    Moya, Francisco
    Vithas Xanit Int Hospital, Spain.
    Bart van der Worp, H.
    University of Medical Centre Utrecht, Netherlands.
    Randall, Gary
    SAFE, England.
    Tsioufis, Konstantinos
    University of Athens, Greece.
    Verhamme, Peter
    University of Leuven, Belgium.
    John Camm, A.
    St Georges University of London, England; Imperial Coll, England.
    Managing reversal of direct oral anticoagulants in emergency situations Anticoagulation Education Task Force White Paper2016Inngår i: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 116, nr 6, s. 1003-1010Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Anticoagulation is the cornerstone of prevention and treatment of venous thromboembolism (VTE) and stroke prevention in patients with atrial fibrillation (AF). However, the mechanisms by which anticoagulants confer therapeutic benefit also increase the risk of bleeding. As such, reversal strategies are critical. Until recently, the direct oral anticoagulants (DOACs) dabigatran, rivaroxaban, apixaban, and edoxaban lacked a specific reversal agent. This report is based on findings from the Anticoagulation Education Task Force, which brought together patient groups and professionals representing different medical specialties with an interest in patient safety and expertise in AF, VTE, stroke, anticoagulation, and reversal agents, to discuss the current status of anticoagulation reversal and fundamental changes in management of bleeding associated with DOACs occasioned by the approval of idarucizumab, a specific reversal agent for dabigatran, as well as recent clinical data on specific reversal agents for factor Xa inhibitors. Recommendations are given for when there is a definite need for a reversal agent (e.g. in cases of life-threatening bleeding, bleeding into a closed space or organ, persistent bleeding despite local haemostatic measures, and need for urgent interventions and/or interventions that carry a high risk for bleeding), when reversal agents may be helpful, and when a reversal agent is generally not needed. Key stakeholders who require 24-7/around-the-clock access to these agents vary among hospitals; however, from a practical perspective the emergency department is recommended as an appropriate location for these agents. Clearly, the advent of new agents requires standardised protocols for treating bleeding on an institutional level.

  • 231. Bestill onlineKjøp publikasjonen >>
    Agholme, Fredrik
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet.
    Wnt signaling and metaphyseal bone healing2011Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    This thesis relates to some new aspects on the regulation of bone healing. In the last few years, Wnt-signaling has been shown to play a central role in bone biology. As well as being involved in bone maintenance and repair, Wnt-signaling has been presented as one of the key pathways through which bone responds to mechanical load. Two secreted extracellular inhibitors of Wnt-signaling, sclerostin and dickkopf-1 are potent negative regulators of bone formation.

    Using a rat fracture model we investigated how metaphyseal bone healing is influenced by changes in Wnt-signaling.

    Antibodies were used to suppress levels of sclerostin and dickkopf-1, and thereby increase Wnt-signaling. Primarily, we investigated if those antibody treatments lead to improved bone healing. Also, we investigated if the response was coupled to the loading conditions of the bone.

    Our findings suggest that suppression of either sclerostin or dickkopf-1 leads to increased bone formation and improved bone healing. Apart from just having an effect on healing, the treatment also improved bone formation in other parts of the skeleton. Depending on the loading conditions, the effects were different. Dickkopf-1 appeared to have a stronger effect on bone volume density in unloaded bone, implying a role mainly in mechano-transduction, while sclerostin had similar effect in both loaded and unloaded bone. To confirm these findings, we studied how the expression of several Wnt-related genes changed due to trauma and unloading in metaphyseal bone. We found that trauma led to upregulation of most of the genes with the largest effect seen in the unloaded bone. In untraumatized bone, there was mainly an effect on the sclerostin gene.

    In conclusion, antibodies against sclerostin and dickkopf-1 appear to be able to improve metaphyseal bone healing. There appear to be some differences in how the effect of the two antibodies manifests itself, especially if the loading conditions of the bone are altered. These findings suggest a potential for clinical use to shorten fracture healing time.

    Delarbeid
    1. Sclerostin Antibody Treatment Enhances Metaphyseal Bone Healing in Rats
    Åpne denne publikasjonen i ny fane eller vindu >>Sclerostin Antibody Treatment Enhances Metaphyseal Bone Healing in Rats
    Vise andre…
    2010 (engelsk)Inngår i: JOURNAL OF BONE AND MINERAL RESEARCH, ISSN 0884-0431, Vol. 25, nr 11, s. 2412-2418Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Sclerostin is the product of the SOST gene Loss of-function mutations in the SOST gene result in a high bone-mass phenotype demonstrating that sclerostin is a negative regulator of bone mass Primarily expressed by osteocytes in bone sclerostin is reported to bind the LRP5/6 receptor thereby antagonizing canonical Wnt signaling and negatively regulating bone formation We therefore investigated whether systemic administration of a sclerostin neutralizing antibody would increase the regeneration of traumatized metaphyseal bone in rats Young male rats had a screw inserted in the proximal tibia and were divided into six groups given 25 mg/kg of sclerostin antibody or control twice a week subcutaneously for 2 or 4 weeks In four groups, the screws were tested for pull out strength At the time of euthanasia a similar screw also was inserted in the contralateral tibia and pull-out tested immediately Sclerostin antibody significantly increased the pull out force by almost 50% compared with controls after 2 and 4 weeks Also the screws inserted at the time of euthanasia showed increased pull out force Micro-computed tomography (mu CT) of the remaining two groups showed that the antibody led to a 30% increase in bone volume fraction in a region surrounding the screw There also was a general increase in trabecular thickness in cancellous bone Thus as measured by the amount of bone and its mechanical resistance the sclerostin antibody increased bone formation during metaphyseal repair but also in untraumatized bone

    sted, utgiver, år, opplag, sider
    American Society for Bone and Mineral Research, 2010
    Emneord
    bone formation;implants;bone repair;sclerostin;antibody
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-62733 (URN)10.1002/jbmr.135 (DOI)000284133500016 ()20499342 (PubMedID)
    Tilgjengelig fra: 2010-12-03 Laget: 2010-12-03 Sist oppdatert: 2011-10-10
    2. The effects of Dickkopf-1 antibody on metaphyseal bone and implant fixation under different loading conditions
    Åpne denne publikasjonen i ny fane eller vindu >>The effects of Dickkopf-1 antibody on metaphyseal bone and implant fixation under different loading conditions
    2011 (engelsk)Inngår i: BONE, ISSN 8756-3282, Vol. 48, nr 5, s. 988-996Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The secreted protein Dickkopf-1 (Dkk1) is an antagonist of canonical Wnt signaling, expressed during fracture healing. It is unclear how it is involved in the mechanical control of bone maintenance. We investigated the response to administration of a Dkk1 neutralizing antibody (Dkk1-ab) in metaphyseal bone under different loading conditions, with or without trauma. In this three part experiment, 120 rats had a screw or bone chamber inserted either unilaterally or bilaterally in the proximal tibia. Mechanical (pull-out) testing, mu CT and histology were used for evaluation. The animals were injected with either 10 mg/kg Dkk1-ab or saline every 14 days for 14, 28, or 42 days. Antibody treatment increased bone formation around the screws and improved their fixation. After 28 days, the pull-out force was increased by over 100%. In cancellous bone, the bone volume fraction was increased by 50%. In some animals, one hind limb was paralyzed with Botulinum toxin A (Botox) to create a mechanically unloaded environment. This did not increase the response to antibody treatment with regard to screw fixation, but in cancellous bone, the bone volume fraction increased by 233%. Thus, the response in unloaded, untraumatized bone was proportionally larger, suggesting that Dkk1 may be up-regulated in unloaded bone. There was also an increase in thickness of the metaphyseal cortex. In bone chambers, the antibody treatment increased the bone volume fraction. The results suggest that antibodies blocking Dkk1 might be used to stimulate bone formation especially during implant fixation, fracture repair, or bone disuse. It also seems that Dkk1 is up-regulated both after metaphyseal trauma and after unloading, and that Dkk1 is involved in mechano-transduction.

    sted, utgiver, år, opplag, sider
    Elsevier Science B.V., Amsterdam., 2011
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-68352 (URN)10.1016/j.bone.2011.02.008 (DOI)000289879900005 ()
    Merknad
    Original Publication: Fredrik Agholme, Hanna Isaksson, Stuart Kuhstoss and Per Aspenberg, The effects of Dickkopf-1 antibody on metaphyseal bone and implant fixation under different loading conditions, 2011, BONE, (48), 5, 988-996. http://dx.doi.org/10.1016/j.bone.2011.02.008 Copyright: Elsevier Science B.V., Amsterdam. http://www.elsevier.com/ Tilgjengelig fra: 2011-05-20 Laget: 2011-05-20 Sist oppdatert: 2011-10-10
    3. Anti-sclerostin antibody and mechanical loading appear to influence metaphyseal bone independently in rats
    Åpne denne publikasjonen i ny fane eller vindu >>Anti-sclerostin antibody and mechanical loading appear to influence metaphyseal bone independently in rats
    Vise andre…
    2011 (engelsk)Inngår i: Acta Orthopaedica, ISSN 1745-3674, Vol. 82, nr 5, s. 628-632Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background and purpose: Sclerostin is produced by osteocytes and is an inhibitor of bone formation. Thus, inhibition of sclerostin by a monoclonal antibody increases bone formation and improves fracture repair. Sclerostin expression is upregulated in unloaded bone and is downregulated by loading. We wanted to determine whether an anti-sclerostin antibody would stimulate metaphyseal healing in unloaded bone in a rat model.

    Methods: 10-week-old male rats (n = 48) were divided into 4 groups, with 12 in each. In 24 rats, the right hind limb was unloaded by paralyzing the calf and thigh muscles with an injection of botulinum toxin A (Botox). 3 days later, all the animals had a steel screw inserted into the right proximal tibia. Starting 3 days after screw insertion, either anti-sclerostin antibody (Scl-Ab) or saline was given twice weekly. The other 24 rats did not receive Botox injections and they were treated with Scl-Ab or saline to serve as normal-loaded controls. Screw pull-out force was measured 4 weeks after insertion, as an indicator of the regenerative response of bone to trauma.

    Results: Unloading reduced the pull-out force. Scl-Ab treatment increased the pull-out force, with or without unloading. The response to the antibody was similar in both groups, and no statistically significant relationship was found between unloading and antibody treatment. The cancellous bone at a distance from the screw showed changes in bone volume fraction that followed the same pattern as the pull-out force.

    Interpretation: Scl-Ab increases bone formation and screwfixation to a similar degree in loaded and unloaded bone.

    sted, utgiver, år, opplag, sider
    Taylor and Francis, 2011
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-71284 (URN)10.3109/17453674.2011.625539 (DOI)
    Tilgjengelig fra: 2011-10-10 Laget: 2011-10-10 Sist oppdatert: 2014-10-17bibliografisk kontrollert
    4. Wnt gene expression during metaphyseal bone healing under different load conditions
    Åpne denne publikasjonen i ny fane eller vindu >>Wnt gene expression during metaphyseal bone healing under different load conditions
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Bone Wnt signalling has been presented as one of the key pathways through which bone responds to mechanical load. This pathway is also active during the healing process after bone trauma. Bone healing can be improved by pharmacological modulation of Wnt signalling. We investigated how the expression of several Wntrelated genes changed due to trauma and unloading in metaphyseal bone.

    20 male rats had one hind limb unloaded by intramuscular Botox injections. In half of the animals a hole was drilled bilaterally in the proximal tibia. After 7 days, a cylindrical biopsy was taken from the bone surrounding the hole and at a corresponding site in animals without trauma. The biopsies were analyzed for the mRNA expression of Wnt1, Wnt3a, Wnt4, Wnt5a, Wnt5b, Sost, Dkk1, Dkk2, Sfrp1, Sfrp4, Lrp5, Lrp6, Wisp1, Wif1 and Wnt10b.

    Trauma led to upregulation of most of the studied genes. This effect was most evident in unloaded bone, where 8 genes were upregulated, among them Wnt receptors, ligands and inhibitors. Unloading increased the expression of Sost in untraumatized bone, but did not significantly influence the other genes.

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-71285 (URN)
    Tilgjengelig fra: 2011-10-10 Laget: 2011-10-10 Sist oppdatert: 2011-10-10bibliografisk kontrollert
    Fulltekst (pdf)
    Wnt signaling and metaphyseal bone healing
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  • 232.
    Agholme, Fredrik
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet.
    Andersson, Therese
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Tengvall, P
    University of Gothenburg.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Local bisphosphonate release versus hydroxyapatite coating for stainless steel screw fixation in rat tibiae2012Inngår i: Journal of materials science. Materials in medicine, ISSN 0957-4530, E-ISSN 1573-4838, Vol. 23, nr 3, s. 743-752Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Implant fixation in bone can be improved by a coating that delivers bisphosphonates locally, or by a hydroxyapatite (HA) coating. In this study, we compared these different types of coatings. For mechanical testing, 30 rats were assigned into three groups, and similar screws were implanted bilaterally in the proximal tibiae. The rats received screws that were either uncoated, coated with nano-crystalline hydroxyapatite or coated with a bisphosphonate releasing protein matrix. After 4 weeks, one screw was subjected to pull-out testing, and the contra-lateral one to torsion testing. For morphology, 30 rats were assigned to similar treatment groups, but received only one screw each. Bisphosphonates enhanced the pull-out force by 41% (P = 0.02) compared to controls, HA increased the pull-out force although not significantly. Conversely, HA increased the maximal torque by 64% (P = 0.02). Morphometry showed higher bone volume around bisphosphonate screws in comparison to HA-coated screws (P andlt; 0.001) and controls (P andlt; 0.001). The results suggest that bisphosphonates improve fixation by increasing the amount of surrounding bone, whereas HA mainly improves bone to implant attachment.

  • 233.
    Agholme, Fredrik
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet.
    Andersson, Therese
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Tengvall, Pentti
    University of Gothenburg.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Ortopedicentrum, Ortopedkliniken Linköping.
    A win for bisphosphonates? Comparison between local bisphosphonate release and hydroxyapatite coating for screw fixation in rats in BONE, vol 46, issue , pp S67-S672010Inngår i: BONE, Elsevier Science B.V., Amsterdam. , 2010, Vol. 46, s. S67-S67Konferansepaper (Fagfellevurdert)
    Abstract [en]

    n/a

  • 234.
    Agholme, Fredrik
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Ortopedicentrum, Ortopedkliniken Linköping.
    Experimental results of combining bisphosphonates with allograft in a rat model2009Inngår i: Journal of Bone and Joint Surgery - Series B, ISSN 0301-620X, Vol. 91, nr 5, s. 670-675Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Soaking bone grafts in a bisphosphonate solution before implantation can prevent their resorption and increase the local bone density in rats and humans. However, recent studies suggest that pre-treatment of allografts with bisphosphonate can prevent bone ingrowth into impaction grafts. We tested the hypothesis that excessive amounts of bisphosphonate would also cause a negative response in less dense grafts. We used a model where nonimpacted metaphyseal bone grafts were randomised into three groups with either no bisphosphonate, alendronate followed by rinsing, and alendronate without subsequent rinsing, and inserted into bone chambers in rats. The specimens were evaluated histologically at one week, and by histomorphometry and radiology at four weeks. At four weeks, both bisphosphonate groups showed an increase in the total bone content, increased newly formed bone, and higher radiodensity than the controls. In spite of being implanted in a chamber with a limited opportunity to diffuse, even an excessive amount of bisphosphonate improved the outcome. We suggest that the negative results seen by others could be due to the combination of densely compacted bone and a bisphosphonate. We suggest that bisphosphonates are likely to have a negative influence where resorption is a prerequisite to create space for new bone ingrowth.

  • 235.
    Agholme, Fredrik
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Ortopedicentrum, Ortopedkliniken Linköping.
    Reduced serum serotonin impairs metaphyseal repair in rats in BONE, vol 46, issue , pp S67-S672010Inngår i: BONE, Elsevier Science B.V., Amsterdam. , 2010, Vol. 46, s. S67-S67Konferansepaper (Fagfellevurdert)
    Abstract [en]

    n/a

  • 236.
    Agholme, Fredrik
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Wnt signaling and orthopedics, an overview2011Inngår i: ACTA ORTHOPAEDICA, ISSN 1745-3674, Vol. 82, nr 2, s. 125-130Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Wnt signaling is a ubiquitous system for intercellular communication, with multiple functions during development and in homeostasis of the body. It comprises several ligands, receptors, and inhibitors. Some molecules, such as sclerostin, appear to have bone-specific functions, and can be targeted by potential drugs. Now, ongoing clinical trials are testing these drugs as treatments for osteoporosis. Animal studies have also suggested that these drugs can accelerate fracture healing and implant fixation. This brief overview focuses on currently available information on the effects of manipulations of Wnt signaling on bone healing.

    Fulltekst (pdf)
    FULLTEXT01
  • 237.
    Agholme, Fredrik
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet.
    Isaksson, Hanna
    Department of Applied Physics, University of Eastern Finland, Kuopio, Finland.
    Kuhstoss, Stuart
    Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, USA.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    The effects of Dickkopf-1 antibody on metaphyseal bone and implant fixation under different loading conditions2011Inngår i: BONE, ISSN 8756-3282, Vol. 48, nr 5, s. 988-996Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The secreted protein Dickkopf-1 (Dkk1) is an antagonist of canonical Wnt signaling, expressed during fracture healing. It is unclear how it is involved in the mechanical control of bone maintenance. We investigated the response to administration of a Dkk1 neutralizing antibody (Dkk1-ab) in metaphyseal bone under different loading conditions, with or without trauma. In this three part experiment, 120 rats had a screw or bone chamber inserted either unilaterally or bilaterally in the proximal tibia. Mechanical (pull-out) testing, mu CT and histology were used for evaluation. The animals were injected with either 10 mg/kg Dkk1-ab or saline every 14 days for 14, 28, or 42 days. Antibody treatment increased bone formation around the screws and improved their fixation. After 28 days, the pull-out force was increased by over 100%. In cancellous bone, the bone volume fraction was increased by 50%. In some animals, one hind limb was paralyzed with Botulinum toxin A (Botox) to create a mechanically unloaded environment. This did not increase the response to antibody treatment with regard to screw fixation, but in cancellous bone, the bone volume fraction increased by 233%. Thus, the response in unloaded, untraumatized bone was proportionally larger, suggesting that Dkk1 may be up-regulated in unloaded bone. There was also an increase in thickness of the metaphyseal cortex. In bone chambers, the antibody treatment increased the bone volume fraction. The results suggest that antibodies blocking Dkk1 might be used to stimulate bone formation especially during implant fixation, fracture repair, or bone disuse. It also seems that Dkk1 is up-regulated both after metaphyseal trauma and after unloading, and that Dkk1 is involved in mechano-transduction.

    Fulltekst (pdf)
    fulltext
  • 238.
    Agholme, Fredrik
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet.
    Isaksson, Hanna
    Department of Applied physics, University of Eastern Finland, Kuopio, Finland.
    Li, Xiaodong
    Metabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
    Ke, Hua Zhu
    Metabolic Disorders, Amgen Inc., Thousand Oaks, CA, USA.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Anti-sclerostin antibody and mechanical loading appear to influence metaphyseal bone independently in rats2011Inngår i: Acta Orthopaedica, ISSN 1745-3674, Vol. 82, nr 5, s. 628-632Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background and purpose: Sclerostin is produced by osteocytes and is an inhibitor of bone formation. Thus, inhibition of sclerostin by a monoclonal antibody increases bone formation and improves fracture repair. Sclerostin expression is upregulated in unloaded bone and is downregulated by loading. We wanted to determine whether an anti-sclerostin antibody would stimulate metaphyseal healing in unloaded bone in a rat model.

    Methods: 10-week-old male rats (n = 48) were divided into 4 groups, with 12 in each. In 24 rats, the right hind limb was unloaded by paralyzing the calf and thigh muscles with an injection of botulinum toxin A (Botox). 3 days later, all the animals had a steel screw inserted into the right proximal tibia. Starting 3 days after screw insertion, either anti-sclerostin antibody (Scl-Ab) or saline was given twice weekly. The other 24 rats did not receive Botox injections and they were treated with Scl-Ab or saline to serve as normal-loaded controls. Screw pull-out force was measured 4 weeks after insertion, as an indicator of the regenerative response of bone to trauma.

    Results: Unloading reduced the pull-out force. Scl-Ab treatment increased the pull-out force, with or without unloading. The response to the antibody was similar in both groups, and no statistically significant relationship was found between unloading and antibody treatment. The cancellous bone at a distance from the screw showed changes in bone volume fraction that followed the same pattern as the pull-out force.

    Interpretation: Scl-Ab increases bone formation and screwfixation to a similar degree in loaded and unloaded bone.

  • 239.
    Agholme, Fredrik
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet.
    Li, Xiaodong
    Amgen Inc.
    Isaksson, Hanna
    University of Eastern Finland.
    Zhu Ke, Hua
    Amgen Inc.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Sclerostin Antibody Treatment Enhances Metaphyseal Bone Healing in Rats2010Inngår i: JOURNAL OF BONE AND MINERAL RESEARCH, ISSN 0884-0431, Vol. 25, nr 11, s. 2412-2418Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Sclerostin is the product of the SOST gene Loss of-function mutations in the SOST gene result in a high bone-mass phenotype demonstrating that sclerostin is a negative regulator of bone mass Primarily expressed by osteocytes in bone sclerostin is reported to bind the LRP5/6 receptor thereby antagonizing canonical Wnt signaling and negatively regulating bone formation We therefore investigated whether systemic administration of a sclerostin neutralizing antibody would increase the regeneration of traumatized metaphyseal bone in rats Young male rats had a screw inserted in the proximal tibia and were divided into six groups given 25 mg/kg of sclerostin antibody or control twice a week subcutaneously for 2 or 4 weeks In four groups, the screws were tested for pull out strength At the time of euthanasia a similar screw also was inserted in the contralateral tibia and pull-out tested immediately Sclerostin antibody significantly increased the pull out force by almost 50% compared with controls after 2 and 4 weeks Also the screws inserted at the time of euthanasia showed increased pull out force Micro-computed tomography (mu CT) of the remaining two groups showed that the antibody led to a 30% increase in bone volume fraction in a region surrounding the screw There also was a general increase in trabecular thickness in cancellous bone Thus as measured by the amount of bone and its mechanical resistance the sclerostin antibody increased bone formation during metaphyseal repair but also in untraumatized bone

  • 240.
    Agholme, Fredrik
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Macias, Brandon
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet.
    Hamang, Matt
    Lilly Research Labs, IN USA .
    Lucchesi, Jonathan
    Lilly Research Labs, IN USA .
    Adrian, Mary D.
    Lilly Research Labs, IN USA .
    Kuhstoss, Stuart
    Lilly Research Labs, IN USA .
    Harvey, Anita
    Lilly Research Labs, IN USA .
    Sato, Masahiko
    Lilly Research Labs, IN USA .
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Efficacy of a Sclerostin Antibody Compared to a Low Dose of PTH on Metaphyseal Bone Healing2014Inngår i: Journal of Orthopaedic Research, ISSN 0736-0266, E-ISSN 1554-527X, Vol. 32, nr 3, s. 471-476Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We compared the effect of a sclerostin antibody to that of a clinically relevant dose of parathyroid hormone (PTH) in a rat model for metaphyseal bone healing. Screws of steel or poly methyl methacrylate (PMMA) were inserted bilaterally into the proximal tibia of young male rats. During 4 weeks the animals then received injections of either phosphate buffered saline (control), sclerostin antibody (25mg/kg, twice weekly) or PTH (5 mu g/kg, daily). The healing response around the screws was then assessed by mechanical testing and X-ray microtomography (mu CT). To distinguish between effects on healing and general effects on the skeleton, other untraumatized bone sites and serum biomarkers were also assessed. After 4 weeks of treatment, PTH yielded a 48% increase in screw pull-out force compared to control (p=0.03), while the antibody had no significant effect. In contrast, the antibody increased femoral cortical and vertebral strength where PTH had no significant effect. mu CT showed only slight changes that were statistically significant for the antibody mainly at cortical sites. The results suggest that a relatively low dose of PTH stimulates metaphyseal repair (screw fixation) specifically, whereas the sclerostin antibody has wide-spread effects, mainly on cortical bone, with less influence on metaphyseal healing.

    Fulltekst (pdf)
    fulltext
  • 241.
    Agholme, Fredrik
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet.
    Sandberg, Olof
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet.
    Aspenberg, Per
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Ortopedi och idrottsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Centrum för kirurgi, ortopedi och cancervård, Ortopedkliniken i Linköping.
    Wnt gene expression during metaphyseal bone healing under different load conditionsManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Bone Wnt signalling has been presented as one of the key pathways through which bone responds to mechanical load. This pathway is also active during the healing process after bone trauma. Bone healing can be improved by pharmacological modulation of Wnt signalling. We investigated how the expression of several Wntrelated genes changed due to trauma and unloading in metaphyseal bone.

    20 male rats had one hind limb unloaded by intramuscular Botox injections. In half of the animals a hole was drilled bilaterally in the proximal tibia. After 7 days, a cylindrical biopsy was taken from the bone surrounding the hole and at a corresponding site in animals without trauma. The biopsies were analyzed for the mRNA expression of Wnt1, Wnt3a, Wnt4, Wnt5a, Wnt5b, Sost, Dkk1, Dkk2, Sfrp1, Sfrp4, Lrp5, Lrp6, Wisp1, Wif1 and Wnt10b.

    Trauma led to upregulation of most of the studied genes. This effect was most evident in unloaded bone, where 8 genes were upregulated, among them Wnt receptors, ligands and inhibitors. Unloading increased the expression of Sost in untraumatized bone, but did not significantly influence the other genes.

  • 242. Bestill onlineKjøp publikasjonen >>
    Agholme, Lotta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Geriatrik. Linköpings universitet, Hälsouniversitetet.
    The involvement of degradation pathways and neuron-to-neuron transmission in Alzheimer’s disease2012Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Although the vast majority of Alzheimer’s disease (AD) cases are of the sporadic type, mutations causing the familial form have been the focus of AD research for decades. The disease is pathologically characterised by β-amyloid (Aβ) and tau protein aggregates in neuritic plaques and neurofibrillary tangles. Furthermore, it is known that AD pathology spreads throughout the brain, most often along the same anatomical pattern. However, so far no cause for the sporadic form of the disease has been found. Accumulation of protein aggregates as well as decreased activity of the protein degradation systems, lysosomes and proteasomes, is found in diseased brains. This indicates that defective degradation contributes to sporadic AD.

    The aim of this thesis was to develop an improved neuronal model, and study the effects of decreased proteasome function on tau phosphorylation and axonal transport. In addition, the effects on Aβ accumulation and generation upon proteasome inhibition were investigated. Finally, the possibility that intracellularly accumulated Aβ oligomers could be transferred from one neuron to another was tested.

    Differentiation of human SH-SY5Y neuroblastoma cells in an extracellular matrix gel, using a set of neurotrophic factors, resulted in cells with neuronal phenotype, expressing neuron specific markers and all six adult isoforms of tau. Within this neuronal model, we found that reduced proteasome activity inhibited neuritic transport, and caused tau phosphorylation in a c-Jun and ERK 1/2 dependent manner. Using proteasome inhibition in APP overexpressing cells, we found an autophagy dependent intralysosomal Aβ accumulation, together with elevation of intra- and extracellular concentrations of Aβ. Autophagy inhibition protected the cells from the toxicity induced by decreased proteasome activity. Finally, we could, as the first group, show that Aβ can be directly transferred from one neuron to another through connected neurites. Furthermore, accumulation of Aβ in the endo-lysosomal compartment of receiving cells caused toxicity and neurodegeneration.

    We believe that cells not able to degrade accumulated Aβ, due to increased generation or reduced degradative capacity, instead tries to clear its content through transfer to connected neurons. If not properly degraded in the receiving cell, this can accelerate AD pathology and cause neuritic and neuronal degeneration spreading throughout the brain. Increasing the activity of the degradative systems, or inhibiting transmission of Aβ between neurons could therefore be novel treatments for AD.

    Delarbeid
    1. An In Vitro Model for Neuroscience: Differentiation of SH-SY5Y Cells into Cells with Morphological and Biochemical Characteristics of Mature Neurons
    Åpne denne publikasjonen i ny fane eller vindu >>An In Vitro Model for Neuroscience: Differentiation of SH-SY5Y Cells into Cells with Morphological and Biochemical Characteristics of Mature Neurons
    Vise andre…
    2010 (engelsk)Inngår i: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 20, nr 4, s. 1069-1082Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Neuroscience, including research on Alzheimers disease, is hampered by the lack of suitable in vitro models to study the human nervous system. To counteract this, many attempts to differentiate cell lines into more neuron-like cells have been performed, resulting in partial expression of neuronal features. Furthermore, it has been reported that neuroblastoma cell lines lack mature isoforms of tau. Our aim was to develop an improved in vitro model, generating sustainable cells with morphology and biochemistry of human, mature neurons. To obtain cells with neuronal differentiation and function, we investigated the effect of combining three-dimensional culturing of SH-SY5Y cells in extracellular matrix (ECM) gel with several factors reported to have neuro-differentiating effects. This resulted in cells with apparent neuronal morphology with long, extensively branched neurites. Further investigation revealed expression of several neurospecific markers including synapse protein Sv2 and nuclear marker NeuN, as well as the presence of synapses and axonal vesicle transport. In addition, these cells expressed mature tau isoforms, and tau protein expression was significantly increased compared to undifferentiated cells, reaching levels found in adult human brain. In conclusion, we found that pre-treatment with retinoic acid followed by ECM gel culturing in combination with brain derived neurotrophic factor, neuregulin beta(1), nerve growth factor, and vitamin D-3 treatment generated sustainable cells with unambiguous resemblance to adult neurons. These cells also expresses adult splicing forms of tau with neuronal localization, making this cellular in vitro model useful in many areas of neuroscience research, particularly the Alzheimers disease field.

    sted, utgiver, år, opplag, sider
    Ios Press, 2010
    Emneord
    Alzheimers disease; differentiation; in vitro model; neuroblastoma; tau
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-58227 (URN)10.3233/JAD-2010-091363 (DOI)000279539500012 ()
    Merknad
    Original Publication: Lotta Agholme, Tobias Lindström, Katarina Kågedal, Jan Marcusson and Martin Hallbeck, An In Vitro Model for Neuroscience: Differentiation of SH-SY5Y Cells into Cells with Morphological and Biochemical Characteristics of Mature Neurons, 2010, Journal of Alzheimer's Disease, (20), 4, 1069-1082. http://dx.doi.org/10.3233/JAD-2010-091363 Copyright: Ios Press http://www.iospress.nl/ Tilgjengelig fra: 2010-08-10 Laget: 2010-08-09 Sist oppdatert: 2019-10-14
    2. Proteasome Inhibition Induces Stress Kinase Dependent Transport Deficits – Implications for Alzheimer’s Disease
    Åpne denne publikasjonen i ny fane eller vindu >>Proteasome Inhibition Induces Stress Kinase Dependent Transport Deficits – Implications for Alzheimer’s Disease
    Vise andre…
    2014 (engelsk)Inngår i: Molecular and Cellular Neuroscience, ISSN 1044-7431, E-ISSN 1095-9327, Vol. 58, s. 29-39Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Alzheimer’s disease (AD) is characterized by accumulation of two misfolded and aggregated proteins, β-amyloid and hyperphosphorylated tau. Both cellular systems responsible for clearance of misfolded and aggregated proteins, the lysosomal and the proteasomal, have been shown to be malfunctioning in the aged brain and more so in AD patients. This malfunction could be the cause of β-amyloid and tau accumulation, eventually aggregating in plaques and tangles. We have investigated how decreased proteasome activity affects AD related pathophysiological changes of microtubule transport and stability, as well as tau phosphorylation. To do this, we used our recently developed neuronal model where human SH-SY5Y cells obtain neuronal morphology and function through differentiation. We found that exposure to low doses of the proteasome inhibitor MG-115 caused disturbed neuritic transport, together with microtubule destabilization and tau phosphorylation. Furthermore, reduced proteasome activity activated several kinases implicated in AD pathology, including JNK, c-Jun and ERK 1/2. Restoration of the microtubule transport was achieved by inhibiting ERK 1/2 activation, and simultaneous inhibition of both ERK 1/2 and c-Jun reversed the proteasome inhibition-induced tau phosphorylation. Taken together, this study suggests that a decrease in proteasome activity can, through activation of c-Jun and ERK 1/2, result in several events contributing to AD pathology. Restoring proteasome function or inhibiting ERK 1/2 and c-Jun could therefore be used as novel treatments against AD.

    sted, utgiver, år, opplag, sider
    Elsevier, 2014
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-81339 (URN)10.1016/j.mcn.2013.11.001 (DOI)000331853600004 ()
    Tilgjengelig fra: 2012-09-12 Laget: 2012-09-12 Sist oppdatert: 2019-10-14bibliografisk kontrollert
    3. Amyloid-β Secretion, Generation, and Lysosomal Sequestration in Response to Proteasome Inhibition: Involvement of Autophagy
    Åpne denne publikasjonen i ny fane eller vindu >>Amyloid-β Secretion, Generation, and Lysosomal Sequestration in Response to Proteasome Inhibition: Involvement of Autophagy
    Vise andre…
    2012 (engelsk)Inngår i: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 31, nr 2, s. 343-358Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    The proteasome is important for degradation of worn out and misfolded proteins. Decreased proteasome activity has been implicated in Alzheimer's disease (AD). Proteasome inhibition induces autophagy, but it is still unknown whether autophagy is beneficial or deleterious to AD neurons, as the autophagosome has been suggested as a site of amyloid-β (Aβ) generation. In this study, we investigated the effect of proteasome inhibition on Aβ accumulation and secretion, as well as the processing of amyloid-β protein precursor (AβPP) in AβPPSwe transfected SH-SY5Y neuroblastoma cells. We show that proteasome inhibition resulted in autophagy-dependent accumulation of Aβ in lysosomes, and increased levels of intracellular and secreted Aβ. The enhanced levels of Aβ could not be explained by increased amounts of AβPP. Instead, reduced degradation of the C-terminal fragment of AβPP (C99) by the proteasome makes C99 available for γ-secretase cleavage, leading to Aβ generation. Inhibition of autophagy after proteasome inhibition led to reduced levels of intracellular, but not secreted Aβ, and tended to further increase the C99 to AβPP ratio, supporting involvement of the autophagosome in Aβ generation. Furthermore, proteasome inhibition caused a reduction in cellular viability, which was reverted by inhibition of autophagy. Dysfunction of the proteasome could cause lysosomal accumulation of Aβ, as well as increased generation and secretion of Aβ, which is partly facilitated by autophagy. As a decrease in cellular viability was also detected, it is possible that upregulation of autophagy is an unsuccessful rescue mechanism, which instead of being protective, contributes to AD pathogenesis.

    sted, utgiver, år, opplag, sider
    I O S Press, 2012
    Emneord
    AβPP processing, Alzheimer’s disease, amyloid- peptide, autophagy, cell death, LC-3, lysosome, p70S6K, proteasome
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-81340 (URN)10.3233/JAD-2012-120001 (DOI)000307377300011 ()22555375 (PubMedID)
    Merknad

    funding agencies|foundations of Engqvist, Wiberg, Hedlund, Osterman, and Stohne||Gustav V and Queen Victorias Foundation||Swedish Alzheimers foundation||Ostergotland County Council||Swedish Research Council||

    Tilgjengelig fra: 2012-09-12 Laget: 2012-09-12 Sist oppdatert: 2019-10-14bibliografisk kontrollert
    4. Spreading of Neurodegenerative Pathology via Neuron-to-Neuron Transmission of beta-Amyloid
    Åpne denne publikasjonen i ny fane eller vindu >>Spreading of Neurodegenerative Pathology via Neuron-to-Neuron Transmission of beta-Amyloid
    Vise andre…
    2012 (engelsk)Inngår i: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 32, nr 26, s. 8767-8777Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Alzheimers disease (AD) is the major cause of dementia. During the development of AD, neurofibrillary tangles progress in a fixed pattern, starting in the transentorhinal cortex followed by the hippocampus and cortical areas. In contrast, the deposition of beta-amyloid (A beta) plaques, which are the other histological hallmark of AD, does not follow the same strict spatiotemporal pattern, and it correlates poorly with cognitive decline. Instead, soluble A beta oligomers have received increasing attention as probable inducers of pathogenesis. In this study, we use microinjections into electrophysiologically defined primary hippocampal rat neurons to demonstrate the direct neuron-to-neuron transfer of soluble oligomeric A beta. Additional studies conducted in a human donor-acceptor cell model show that this A beta transfer depends on direct cellular connections. As the transferred oligomers accumulate, acceptor cells gradually show beading of tubulin, a sign of neurite damage, and gradual endosomal leakage, a sign of cytotoxicity. These observations support that intracellular A beta oligomers play a role in neurodegeneration, and they explain the manner in which A beta can drive disease progression, even if the extracellular plaque load is poorly correlated with the degree of cognitive decline. Understanding this phenomenon sheds light on the pathophysiological mechanism of AD progression. Additional elucidation will help uncover the detailed mechanisms responsible for the manner in which AD progresses via anatomical connections and will facilitate the development of new strategies for stopping the progression of this incapacitating disease.

    sted, utgiver, år, opplag, sider
    SOC NEUROSCIENCE, 2012
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-79695 (URN)10.1523/JNEUROSCI.0615-12.2012 (DOI)000305890700003 ()
    Tilgjengelig fra: 2012-08-13 Laget: 2012-08-13 Sist oppdatert: 2019-10-14
    Fulltekst (pdf)
    The involvement of degradation pathways and neuron-to-neuron transmission in Alzheimer’s disease
    Download (pdf)
    omslag
  • 243.
    Agholme, Lotta
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Hallbeck, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för inflammationsmedicin. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Getting rid of intracellular Aβ- loss of cellular degradation leads to transfer between connected neurons2014Inngår i: Current pharmaceutical design, ISSN 1381-6128, E-ISSN 1873-4286, Vol. 20, nr 15, s. 2458-2468Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The sporadic, late onset form of Alzheimers disease (AD) shares pathological hallmarks with the familial form; however, no clear reason for increased beta-amyloid (A beta) generation has been found in the former. It has long been speculated that the late onset form of AD is caused by reduced degradation and/or clearance of A beta. Indeed, both intracellular degradation systems, the proteasomal and lysosomal systems, have been shown to be defective in AD. Reduced proteasome activity increases levels of intracellular and secreted A beta. Furthermore, accumulation of improperly degraded A beta in the lysosomes causes lysosomal disruption and cell death. We recently showed that oligomeric A beta can be transmitted from one neuron to another, which causes neurotoxicity. In both the donating and receiving cells, A beta accumulates in the endo-lysosomal compartment. It is possible that ineffective degradation of A beta causes its transfer to neighboring neurons, thereby spreading AD pathology. This review summarizes the data underlying the idea of reduced A beta clearance and subsequent A beta spread in AD, and also suggests new therapeutic methods, which are aimed at targeting the degradation systems and synaptic transfer. By enhancing degradation of intracellular accumulated A beta, it can be possible to remove it and avoid A beta-induced neurodegeneration without disturbing the endogenously important pool of secreted A beta. Additionally, drugs targeted to inhibit the spread of intracellular toxic A beta aggregates may also be useful in stopping the progression of pathology, without affecting the level of A beta that normally occurs in the brain.

  • 244.
    Agholme, Lotta
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Geriatrik. Linköpings universitet, Hälsouniversitetet.
    Hallbeck, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Benedikz, Eirikur
    Department of Neurobiology, Division of Neurodegeneration, Care Sciences and Society, Karolinska Institute, Stockholm, Sweden.
    Marcusson, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Geriatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Geriatriska kliniken.
    Kågedal, Katarina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet.
    Amyloid-β Secretion, Generation, and Lysosomal Sequestration in Response to Proteasome Inhibition: Involvement of Autophagy2012Inngår i: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 31, nr 2, s. 343-358Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The proteasome is important for degradation of worn out and misfolded proteins. Decreased proteasome activity has been implicated in Alzheimer's disease (AD). Proteasome inhibition induces autophagy, but it is still unknown whether autophagy is beneficial or deleterious to AD neurons, as the autophagosome has been suggested as a site of amyloid-β (Aβ) generation. In this study, we investigated the effect of proteasome inhibition on Aβ accumulation and secretion, as well as the processing of amyloid-β protein precursor (AβPP) in AβPPSwe transfected SH-SY5Y neuroblastoma cells. We show that proteasome inhibition resulted in autophagy-dependent accumulation of Aβ in lysosomes, and increased levels of intracellular and secreted Aβ. The enhanced levels of Aβ could not be explained by increased amounts of AβPP. Instead, reduced degradation of the C-terminal fragment of AβPP (C99) by the proteasome makes C99 available for γ-secretase cleavage, leading to Aβ generation. Inhibition of autophagy after proteasome inhibition led to reduced levels of intracellular, but not secreted Aβ, and tended to further increase the C99 to AβPP ratio, supporting involvement of the autophagosome in Aβ generation. Furthermore, proteasome inhibition caused a reduction in cellular viability, which was reverted by inhibition of autophagy. Dysfunction of the proteasome could cause lysosomal accumulation of Aβ, as well as increased generation and secretion of Aβ, which is partly facilitated by autophagy. As a decrease in cellular viability was also detected, it is possible that upregulation of autophagy is an unsuccessful rescue mechanism, which instead of being protective, contributes to AD pathogenesis.

  • 245.
    Agholme, Lotta
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Geriatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i östra Östergötland, Geriatriska enheten.
    Lindström, Tobias
    Linköpings universitet, Institutionen för klinisk och experimentell medicin. Linköpings universitet, Hälsouniversitetet.
    Kågedal, Katarina
    Linköpings universitet, Institutionen för nervsystem och rörelseorgan, Patologi. Linköpings universitet, Hälsouniversitetet.
    Marcusson, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Geriatrik. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Geriatriska kliniken.
    Hallbeck, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Experimentell patologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Laboratoriemedicinskt centrum, Klinisk patologi och klinisk genetik.
    An In Vitro Model for Neuroscience: Differentiation of SH-SY5Y Cells into Cells with Morphological and Biochemical Characteristics of Mature Neurons2010Inngår i: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 20, nr 4, s. 1069-1082Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Neuroscience, including research on Alzheimers disease, is hampered by the lack of suitable in vitro models to study the human nervous system. To counteract this, many attempts to differentiate cell lines into more neuron-like cells have been performed, resulting in partial expression of neuronal features. Furthermore, it has been reported that neuroblastoma cell lines lack mature isoforms of tau. Our aim was to develop an improved in vitro model, generating sustainable cells with morphology and biochemistry of human, mature neurons. To obtain cells with neuronal differentiation and function, we investigated the effect of combining three-dimensional culturing of SH-SY5Y cells in extracellular matrix (ECM) gel with several factors reported to have neuro-differentiating effects. This resulted in cells with apparent neuronal morphology with long, extensively branched neurites. Further investigation revealed expression of several neurospecific markers including synapse protein Sv2 and nuclear marker NeuN, as well as the presence of synapses and axonal vesicle transport. In addition, these cells expressed mature tau isoforms, and tau protein expression was significantly increased compared to undifferentiated cells, reaching levels found in adult human brain. In conclusion, we found that pre-treatment with retinoic acid followed by ECM gel culturing in combination with brain derived neurotrophic factor, neuregulin beta(1), nerve growth factor, and vitamin D-3 treatment generated sustainable cells with unambiguous resemblance to adult neurons. These cells also expresses adult splicing forms of tau with neuronal localization, making this cellular in vitro model useful in many areas of neuroscience research, particularly the Alzheimers disease field.

    Fulltekst (pdf)
    FULLTEXT01
  • 246.
    Agholme, Lotta
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i östra Östergötland, Geriatriska kliniken ViN.
    Nath, Sangeeta
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet.
    Domert, Jakob
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet.
    Marcusson, Jan
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Närsjukvården i centrala Östergötland, Geriatriska kliniken.
    Kågedal, Katarina
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Hallbeck, Martin
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neurovetenskap. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Proteasome Inhibition Induces Stress Kinase Dependent Transport Deficits – Implications for Alzheimer’s Disease2014Inngår i: Molecular and Cellular Neuroscience, ISSN 1044-7431, E-ISSN 1095-9327, Vol. 58, s. 29-39Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Alzheimer’s disease (AD) is characterized by accumulation of two misfolded and aggregated proteins, β-amyloid and hyperphosphorylated tau. Both cellular systems responsible for clearance of misfolded and aggregated proteins, the lysosomal and the proteasomal, have been shown to be malfunctioning in the aged brain and more so in AD patients. This malfunction could be the cause of β-amyloid and tau accumulation, eventually aggregating in plaques and tangles. We have investigated how decreased proteasome activity affects AD related pathophysiological changes of microtubule transport and stability, as well as tau phosphorylation. To do this, we used our recently developed neuronal model where human SH-SY5Y cells obtain neuronal morphology and function through differentiation. We found that exposure to low doses of the proteasome inhibitor MG-115 caused disturbed neuritic transport, together with microtubule destabilization and tau phosphorylation. Furthermore, reduced proteasome activity activated several kinases implicated in AD pathology, including JNK, c-Jun and ERK 1/2. Restoration of the microtubule transport was achieved by inhibiting ERK 1/2 activation, and simultaneous inhibition of both ERK 1/2 and c-Jun reversed the proteasome inhibition-induced tau phosphorylation. Taken together, this study suggests that a decrease in proteasome activity can, through activation of c-Jun and ERK 1/2, result in several events contributing to AD pathology. Restoring proteasome function or inhibiting ERK 1/2 and c-Jun could therefore be used as novel treatments against AD.

  • 247. Bestill onlineKjøp publikasjonen >>
    Agnafors, Sara
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Västra Götalandsregionen, Södra Älvsborgs Sjukhus, Barn- och ungdomspsykiatriska kliniken.
    A Biopsychosocial and Long Term Perspective on Child Behavioral Problems: Impact of Risk and Resilience2016Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Mental health has become a prominent issue in society. Yet, much remains unknown about the etiology of psychiatric disorders. The aim of the present thesis was to investigate the association between biological, psychological and social factors of risk and resilience and behavioral problems in a birth cohort of Swedish children. 1723 mothers and their children were followed from birth to the age of 12 as part of the South East Sweden Birth Cohort Study (the SESBiC study). Information was gathered through register data, standardized questionnaires and DNA samples.

    In study I, stability of maternal symptoms of depression and the impact on child behavior at age 12 were investigated. The prevalence of depressive symptoms was found to be 12.0 % postpartum. Symptoms of postpartum depression significantly increased the risk for subsequent depressive symptoms 12 years later in women. Children whose mothers reported concurrent symptoms of depression and anxiety had an increased risk for both internalizing and externalizing problems at age 12, but no long term effect on child behavior was seen for postpartum depressive symptoms. The greatest risk was seen for children whose mothers reported symptoms of depression on both occasions. In study II, the impact of gene-environment interaction of 5-HTTLPR and BDNF Val66Met and experience of life events together with symptoms of maternal depression and anxiety on child behavior at age 12 was studied. A main effect of 5-HTTLPR was noticed, but no geneenvironment effects were shown. Similarly to study I, concurrent symptoms of maternal depression and anxiety were an important predictor of child behavioral problems. A high degree of psychosocial stress around childbirth was found to have long lasting detrimental effects on child behavior, increasing the risk for internalizing problems at age 12. Study III investigated the impact of geneenvironment interactions of 5-HTTLPR and BDNF Val66Met and life events together with symptoms of maternal depression and birth characteristics on behavioral problems at age 3. Symptoms of postpartum depression were found to predict internalizing as well as externalizing problems in children three years later. Child experience of life events was a stable predictor of behavioral problems across the scales similar to sociodemographic factors such as parental immigration status and unemployment. No gene-environment interaction effects of 5-HTTLPR or BDNF Val66Met were shown. Study IV used the risk factors identified in studies I-III to investigate factors of resilience to behavioral problems at age 12. The l/l genotype of 5-HTTLPR was associated with a lower risk for behavioral problems at age 12, especially for children facing low adversity. Good social functioning was found to be a general resource factor, independent of the level of risk, while an easy temperament was associated with resilience for children with a high degree of adversity. However, effect sizes were small.

    In summary, the results from the present thesis emphasize the importance of maternal mental health and sociodemographic factors for child mental health at ages 3 and 12, which must be taken into account in clinical settings. Moreover, it adds to the null-findings of the gene-environment effect of 5-HTTLPR and BDNF Val66Met on behavioral problems in children, but indicates a main effect of 5-HTTLPR on internalizing symptoms at age 12.

    Delarbeid
    1. Symptoms of Depression Postpartum and 12 years Later-Associations to Child Mental Health at 12 years of Age
    Åpne denne publikasjonen i ny fane eller vindu >>Symptoms of Depression Postpartum and 12 years Later-Associations to Child Mental Health at 12 years of Age
    2013 (engelsk)Inngår i: Maternal and Child Health Journal, ISSN 1092-7875, E-ISSN 1573-6628, Vol. 17, nr 3, s. 405-414Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Children of depressed mothers have been shown to express behaviour problems to a greater extent than children of non-depressed mothers. The purpose of this study was to examine the persistence of depressive symptoms in mothers and to evaluate the relative importance of symptoms of postpartum depression (PPD) and concurrent maternal symptoms of depression, on child behaviour at age 12. A birth cohort of 1,707 children and their mothers was followed from 3 months after birth to 12 years after birth. Self-reported symptoms of depression in mothers were assessed at baseline and 12-year follow-up where 893 mothers (52.3 %) and their children participated. The mothers reports on the behaviour of their children at age 12 were used. Multivariate analysis was used to assess factors that increased the risk of child behaviour problems. At baseline, 10.4 % scored above the cutoff for symptoms of postpartum depression. At follow up, 18.2 % scored above the cutoff for depressive symptoms. Multivariate analysis showed that ongoing maternal symptoms of depression, as distinct from PPD-symptoms, was the strongest predictor of child behaviour problems at age 12. The gender of the child and socio-demographic factors at baseline were additional factors that affected the risk of behaviour problems in the 12 year old children. Children of mothers who reported symptoms of depression, both postpartum and at follow-up, were at a greater risk of behaviour problems compared to children of women with no depressive symptoms on either occasion. Our findings indicate that recurrent and ongoing maternal depressive symptoms significantly increase the risk of child behaviour problems as reported by mothers, while symptoms of PPD do not seem to result in an increased risk of behaviour problems in 12 year olds. High maternal socio-demographic life stress at childbirth constitutes an important risk factor for later child behaviour problems.

    sted, utgiver, år, opplag, sider
    Springer Verlag (Germany), 2013
    Emneord
    CBCL, Children, Mental health, Postpartum depression, SESBiC-study
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-90750 (URN)10.1007/s10995-012-0985-z (DOI)000316021200003 ()
    Tilgjengelig fra: 2013-04-05 Laget: 2013-04-05 Sist oppdatert: 2017-12-06
    2. Effect of gene, environment and maternal depressive symptoms on pre-adolescence behavior problems - a longitudinal study.
    Åpne denne publikasjonen i ny fane eller vindu >>Effect of gene, environment and maternal depressive symptoms on pre-adolescence behavior problems - a longitudinal study.
    Vise andre…
    2013 (engelsk)Inngår i: Child and Adolescent Psychiatry and Mental Health, ISSN 1753-2000, E-ISSN 1753-2000, Vol. 7, nr 1, s. 10-Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    BACKGROUND: Depression is a common and disabling condition with a high relapse frequency. Maternal mental health problems and experience of traumatic life events are known to increase the risk of behavior problems in children. Recently, genetic factors, in particular gene-by-environment interaction models, have been implicated to explain depressive etiology. However, results are inconclusive.

    METHODS: Study participants were members of the SESBiC-study. A total of 889 mothers and their children were followed during the child's age of 3 months to 12 years. Information on maternal depressive symptoms was gathered postpartum and at a 12 year follow-up. Mothers reported on child behavior and traumatic life events experienced by the child at age 12. Saliva samples were obtained from children for analysis of 5-HTTLPR and BDNF Val66Met polymorphisms.

    RESULTS: Multivariate analysis showed a significant association between maternal symptoms of depression and anxiety, and internalizing problems in 12-year-old children (OR 5.72, 95% CI 3.30-9.91). Furthermore, carriers of two short alleles (s/s) of the 5-HTTLPR showed a more than 4-fold increased risk of internalizing problems at age 12 compared to l/l carriers (OR 4.73, 95% CI 2.14-10.48). No gene-by-environment interaction was found and neither depressive symptoms postpartum or traumatic experiences during childhood stayed significant in the final model.

    CONCLUSIONS: Concurrent maternal symptoms of depression and anxiety are significant risk factors for behavior problems in children, which need to be taken into account in clinical practice. Furthermore, we found a main effect of 5-HTTLPR on internalizing symptoms in 12-year-old children, a finding that needs to be confirmed in future studies.

    sted, utgiver, år, opplag, sider
    BioMed Central, 2013
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-104869 (URN)10.1186/1753-2000-7-10 (DOI)23518193 (PubMedID)
    Tilgjengelig fra: 2014-02-28 Laget: 2014-02-28 Sist oppdatert: 2017-12-05bibliografisk kontrollert
    3. Early predictors of behavioural problems in pre-schoolers: a longitudinal study of constitutional and environmental main and interaction effects
    Åpne denne publikasjonen i ny fane eller vindu >>Early predictors of behavioural problems in pre-schoolers: a longitudinal study of constitutional and environmental main and interaction effects
    Vise andre…
    2016 (engelsk)Inngår i: BMC Pediatrics, ISSN 1471-2431, E-ISSN 1471-2431, Vol. 16Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Background: The early environment is important for child development and wellbeing. Gene-by-environment studies investigating the impact of the serotonin transporter genelinked polymorphic region (5-HTTLPR) and the Brain Derived Neurotrophic Factor (BDNF) Val66Met polymorphisms by life events on mental health and behaviour problems have been inconclusive. Methodological differences regarding sample sizes, study population, definitions of adversities and measures of mental health problems obstacle their comparability. Furthermore, very few studies included children. The aim of this study was to examine the associations between a broad range of risk factors covering pregnancy and birth, genetic polymorphism, experience of multiple life events and psychosocial environment, and child behaviour at age three, using a comparably large, representative, population-based sample.

    Methods: A total of 1,106 children, and their mothers, were followed from pregnancy to age three. Information on pregnancy and birth-related factors was retrieved from the Medical Birth Register. Questionnaires on depressive symptoms, child behaviour and child experiences of life events were filled in by the mothers. Child saliva samples were used for genotyping the 5-HTTLPR and BDNF Val66Met polymorphisms. Multiple logistic regression was used to investigate the association between psychological scales and genetic polymorphisms.

    Results: Symptoms of postpartum depression increased the risk of both internalizing and externalizing problems. Experience of multiple life events was also a predictor of behavioural problems across the scales. No gene-by-environment or gene-bygene-by-environment interactions were found. Children of immigrants had an increased risk of internalizing problems and parental unemployment was significantly associated with both internalizing and externalizing type of problems.

    Conclusion: This study shows the importance of the psychosocial environment for psychosocial health in preschool children, and adds to  the literature of null-findings of gene-by-environment effects of 5-HTTLPR and BDNF in children

    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-124207 (URN)10.1186/s12887-016-0614-x (DOI)000377535800002 ()
    Merknad

    Funding agencies:Funding was obtained from the Swedish Council for Working Life and Social Research (FAS), the Swedish Research Council (VR), the Clas Groschinsky Memorial Foundation, Stockholm, Samariten Foundation, Stockholm, the Hallsten Research Foundation and ALF, County Council of Ostergotland.

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    Tilgjengelig fra: 2016-01-22 Laget: 2016-01-22 Sist oppdatert: 2017-11-30bibliografisk kontrollert
    4. A biopsychosocial approach to risk and resilience on behavior in children followed from birth to age twelve
    Åpne denne publikasjonen i ny fane eller vindu >>A biopsychosocial approach to risk and resilience on behavior in children followed from birth to age twelve
    Vise andre…
    2016 (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    An increasing prevalence of mental health problems calls for more knowledge into factors associated with resilience in the context of child behavior. Biological factors are seldom considered in psychosocial models of resilience. The present study used multiple statistical methodologies to examine a biopsychosocial model of risk and resilience on behavior at preadolescence. Data from 889 children and their mothers were used. A cumulative adversity score was created by combining maternal symptoms of depression, psychosocial risk and children’s experiences of life events. The proposed resilience factors investigated were candidate genetic polymorphisms, child temperament and social functioning, and maternal sense of coherence. Results show that the l/l genotype of the serotonin transporter linked polymorphic region (5-HTTLPR) was associated with lower internalizing scores, especially for children exposed to low adversity. An easy temperament was associated with resilient outcomes for children exposed to high adversity. Child social functioning was found to be more of a general resource variable buffering risk in both high and low adversity groups. The results support a multiple level model of resilience indicating effects, though small, of both biological and psychosocial factors. The present findings call for both preventive actions and further studies on biopsychosocial models in resilience research.

    Emneord
    Child, genotype, longitudinal, mental health, resilience
    HSV kategori
    Identifikatorer
    urn:nbn:se:liu:diva-124208 (URN)
    Tilgjengelig fra: 2016-01-22 Laget: 2016-01-22 Sist oppdatert: 2016-01-22bibliografisk kontrollert
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  • 248.
    Agnafors, Sara
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten.
    Bladh, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Svedin, Carl Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Barnafrid. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Barn- och ungdomspsykiatriska kliniken.
    Sydsjö, Gunilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Mental health in young mothers, single mothers and their children2019Inngår i: BMC Psychiatry, ISSN 1471-244X, E-ISSN 1471-244X, Vol. 19, artikkel-id 112Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Parenthood is a life transition that can be especially demanding for vulnerable individuals. Young maternal age and maternal single status have been reported to increase the risk for adverse outcomes for both mother and child. The aim of this study was to investigate the effect of young maternal age and maternal single status on maternal and child mental health and child development at age 3. Methods: A birth-cohort of 1723 mothers and their children were followed from birth to age 3. Sixty-one mothers (3.5%) were age 20 or younger, and 65 (4.0%) reported single status at childbirth. The mothers filled out standardized instruments and medical information was retrieved from the standardized clinical assessment of the children at Child Welfare Centers, (CWC). Results: Young maternal age was associated with symptoms of postpartum depression whereas single status was not. Young mothers were more prone to report internalizing and externalizing problems in their children, while there was no association between single status and child behavioral problems. No differences were seen on child development (CWC scores). School drop-out was, however, a more influential factor on depressive symptoms postpartum than maternal age. Conclusion: Young mothers are at increased risk for symptoms of postpartum depression which indicates the need for attention in pre- and postnatal health care programs. Single mothers and their children were not found to be at increased risk for adverse outcomes. The importance of schooling was demonstrated, indicating the need for societal support to encourage adolescents to remain in school.

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    fulltext
  • 249.
    Agnafors, Sara
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Barn- och ungdomspsykiatri. Linköpings universitet, Hälsouniversitetet.
    Comasco, Erika
    Division of Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Bladh, Marie
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Obstetrik och gynekologi. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Sydsjö, Gunilla
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet. Östergötlands Läns Landsting, Barn- och kvinnocentrum, Kvinnokliniken i Linköping.
    Dekeyser, Linda
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    Oreland, Lars
    Division of Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden.
    Svedin, Carl Göran
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för kliniska vetenskaper. Linköpings universitet, Hälsouniversitetet.
    Effect of gene, environment and maternal depressive symptoms on pre-adolescence behavior problems - a longitudinal study.2013Inngår i: Child and Adolescent Psychiatry and Mental Health, ISSN 1753-2000, E-ISSN 1753-2000, Vol. 7, nr 1, s. 10-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Depression is a common and disabling condition with a high relapse frequency. Maternal mental health problems and experience of traumatic life events are known to increase the risk of behavior problems in children. Recently, genetic factors, in particular gene-by-environment interaction models, have been implicated to explain depressive etiology. However, results are inconclusive.

    METHODS: Study participants were members of the SESBiC-study. A total of 889 mothers and their children were followed during the child's age of 3 months to 12 years. Information on maternal depressive symptoms was gathered postpartum and at a 12 year follow-up. Mothers reported on child behavior and traumatic life events experienced by the child at age 12. Saliva samples were obtained from children for analysis of 5-HTTLPR and BDNF Val66Met polymorphisms.

    RESULTS: Multivariate analysis showed a significant association between maternal symptoms of depression and anxiety, and internalizing problems in 12-year-old children (OR 5.72, 95% CI 3.30-9.91). Furthermore, carriers of two short alleles (s/s) of the 5-HTTLPR showed a more than 4-fold increased risk of internalizing problems at age 12 compared to l/l carriers (OR 4.73, 95% CI 2.14-10.48). No gene-by-environment interaction was found and neither depressive symptoms postpartum or traumatic experiences during childhood stayed significant in the final model.

    CONCLUSIONS: Concurrent maternal symptoms of depression and anxiety are significant risk factors for behavior problems in children, which need to be taken into account in clinical practice. Furthermore, we found a main effect of 5-HTTLPR on internalizing symptoms in 12-year-old children, a finding that needs to be confirmed in future studies.

    Fulltekst (pdf)
    fulltext
  • 250.
    Agnafors, Sara
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för barns och kvinnors hälsa. Linköpings universitet, Medicinska fakulteten. Sodra Alvsborgs Hosp, Sweden.
    Norman Kjellstrom, Anna
    Reg Vastra Gotaland, Sweden.
    Torgerson, Jarl
    Sahlgrens Univ Hosp, Sweden.
    Rusner, Marie
    Sodra Alvsborgs Hosp, Sweden; Univ Gothenburg, Sweden.
    Somatic comorbidity in children and adolescents with psychiatric disorders2019Inngår i: European Child and Adolescent Psychiatry, ISSN 1018-8827, E-ISSN 1435-165X, Vol. 28, nr 11, s. 1517-1525Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    In the adult population, psychiatric disorders are associated with somatic illness. Explanatory life style factors have been found, but also a failure to recognize somatic illness in this group. Another factor is side effects from long-term use of antipsychotic drugs. Given the psychiatric-somatic comorbidity in the adult population, it is of interest to investigate whether an association exists already during childhood. The aim of the present study was to investigate the frequency of somatic illness in children and adolescents with a psychiatric diagnose. Data were obtained from the regional health care database Vega, Sweden. Psychiatric and somatic diagnoses obtained during 2011-2013 for individuals aged 3-18 years were extracted. Descriptive statistics were used to examine difference in somatic morbidity between children with and without psychiatric diagnoses. Logistic regression was used in age-stratified models to test the association between psychiatric and somatic diagnoses. Anxiety and behavioral disorders were associated with all somatic conditions investigated at nearly all ages. The same applied to substance use, investigated at age 9-18 years. Affective disorders were associated with all somatic conditions at age 12-18 years. Psychotic conditions were associated with asthma, bowel disorders and myalgia in adolescents. Children with psychiatric disorders are at remarkably high risk for concurrent somatic illness. The associations span across many types of conditions and across all ages. The results support the need for awareness of somatic morbidity in child and adolescent psychiatric clinical settings, and the need for coordinated health care for children with comorbid states.

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    fulltext
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