1. |
- Agholme, Fredrik, et al.
(författare)
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Experimental results of combining bisphosphonates with allograft in a rat model
- 2009
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Ingår i: Journal of Bone and Joint Surgery - Series B. - 0301-620X. ; 91:5, s. 670-675
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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2. |
- Andersson, Per, et al.
(författare)
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The Configuration Of Actors In Market Practice
- 2009
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Ingår i: Marketing Theory. - : SAGE Publications (UK and US). - 1741-301X .- 1470-5931. ; 8:1, s. 67-90
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Tidskriftsartikel (refereegranskat)abstract
- This paper addresses three conceptual challenges concerning actors and agency that arise when taking interest in market practice: i) how agency is awarded in practical situations, ii) how actors are preconfigured, and iii) how actors are represented. These issues are explored in three empirical scenes taken from a case study of the introduction of an e-procurement system at an international transport and logistics company. First, we suggest that practical interaction can be fruitfully regarded as a process of interdefinition involving prescriptions and subscriptions between acting entities, or actants . Second, we employ the term inscription to address efforts to affect in advance the configuration of such actants. Third, we suggest that actors are entities to which actions are ascribed, ex post . Through this secondary process a number of actants may be subsumed under a common actor label, thus offering a way of accounting for agency as part of a practice perspective. We conclude by discussing implications of the proposed vocabulary for multiplicity, reflexivity and market agency.
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3. |
- Andersson, Therese, et al.
(författare)
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Tissue memory in healing tendons : short loading episodes stimulate healing
- 2009
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Ingår i: JOURNAL OF APPLIED PHYSIOLOGY. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 107:2, s. 417-421
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Tidskriftsartikel (refereegranskat)abstract
- Intact tendons adapt slowly to changes in mechanical loading, whereas in healing tendons the effect of mechanical loading or its absence is dramatic. The longevity of the response to a single loading episode is, however, unknown. We hypothesized that the tissue has a "memory" of loading episodes and that therefore short loadings are sufficient to elicit improved healing. The Achilles tendon of 70 female rats was transected and unloaded by tail suspension for 12 days (suspension started on day 2 after surgery). Each day, the rats were let down from suspension for short daily training episodes according to different regimes: 15 min of cage activity or treadmill running for 15, 30, 60, or 2 x 15 min. Rats with transected Achilles tendons and full-time cage activity served as controls. The results demonstrated that full-time cage activity increased the peak force over three times compared with unloading. Short daily loading episodes (treadmill running) increased the peak force about half as much as full-time activity. Prolongation of treadmill running above 15 min or dividing the daily training in two separate episodes had minimal further effect. This mechanical stimulation increased the cross-sectional area but had no effect on the mechanical properties of the repair tissue. The findings indicate that once the tissue had received information from a certain loading type and level, this is "memorized" and leads to a response lasting many hours. This suggests that patients might be allowed early short loading episodes following, e. g., an Achilles tendon rupture for a better outcome.
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4. |
- Aspenberg, Per, 1949-, et al.
(författare)
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Additive effects of PTH and bisphosphonates on the bone healing response to metaphyseal implants in rats
- 2008
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 79:1, s. 111-115
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: When PTH is used to increase the amount of bone in osteoporotic patients, combination with bisphosphonates is known to attenuate the response. This might be explained by the reduced number of remodeling sites after bisphosphonate treatment, which reduces the number of cells able to respond to PTH. However, in a repair situation after trauma, a large number of osteoblasts reside in the wound site. If their activity is no longer coupled to osteoclasts, decreased resorption by bisphosphonates and stimulation of osteoblastic activity by PTH should both (independently) increase bone formation. Thus, we hypothesized that in contrast to the case in osteoporosis treatment, PTH and bisphosphonates have an additive effect in situations involving bone regeneration. MATERIAL AND METHODS: Stainless steel screws, either coated with biphosphonates or uncoated, were inserted in 46 rat tibias. This normally elicits a bone repair response, leading to a gradual increase in the strength of screw fixation. Half of the rats also received daily injections of teriparatide (PTH). Thus, there were 4 groups: control, bisphosphonate, PTH, and bisphosphonate plus PTH. Pull-out force and energy were measured after 2 weeks. RESULTS: The combined treatment had the strongest effect. It doubled the pull-out force and tripled the pull-out energy, compared to untreated controls. Also, bisphosphonate or PTH alone increased the pull-out force and energy, although less. No treatment cross-dependency was observed. INTERPRETATION: Because bisphosphonates mainly influence osteoclasts, and intermittent administration of PTH mainly influences osteoblasts, our findings indicate that to a large extent these cells work without coupling in this model. It appears that bisphosphonates are unlikely to attenuate the response to PTH during the formation of new bone.
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5. |
- Aspenberg, Per
(författare)
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Bisphosphonates and implants
- 2009
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Ingår i: Acta orthopaedica. - : Medical Journals Sweden AB. - 1745-3682 .- 1745-3674. ; 80:1, s. 119-123
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Tidskriftsartikel (refereegranskat)
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6. |
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7. |
- Aspenberg, Per
(författare)
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Drugs and fracture repair
- 2005
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 76:6, s. 741-748
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Forskningsöversikt (refereegranskat)
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8. |
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9. |
- Aspenberg, Per, 1949-
(författare)
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Editorial: Is inflammation harmless to loaded tendons?
- 2007
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Ingår i: Journal of applied physiology. - : American Psychological Association (APA). - 8750-7587 .- 1522-1601. ; 102:1, s. 3-4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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10. |
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11. |
- Aspenberg, Per, 1949-
(författare)
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Editorial: Osteonecrosis of the jaw : What do bisphosphonates do?
- 2006
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Ingår i: Expert Opinion on Drug Safety. - : Informa Healthcare. - 1474-0338 .- 1744-764X. ; 5:6, s. 743-745
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Osteonecrosis of the jaw is a new disease, partly caused by bisphosphonates. It is commonly assumed that the bisphosphonates somehow cause cell death (osteocyte necrosis) within the jawbone, which makes it prone to chronic infection. In this article, an alternative pathogenetic theory is suggested, based on the normal effect of bisphosphonates. According to the new theory, the bone is alive until it is injured and infected, and the reduced resorptive ability due to bisphosphonates hinders the formation of a fresh bone surface for re-establishment of bone cell coverage. The theories are compared, based on the recent, very scarce literature. None of them can be completely refuted, but the demonstration of living osteocytes within the lesion and the number of necessary assumptions speak against the theory of a primary, bisphosphonate-induced necrosis.
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12. |
- Aspenberg, Per, 1949-, et al.
(författare)
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Fixed or loose? Dichotomy in RSA data for cemented cups
- 2008
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Ingår i: Acta Orthopaedica. - Basingstoke : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 79:4, s. 467-473
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Roentgen stereometric analysis (RSA) cannot discern whether a single prosthesis is fixed or migrating below the detection level. Samples of patients usually show migration values that appear to be continuously distributed. Is there such continuity, or is there a dichotomy between stable and migrating prostheses? The hypothesis of a dichotomy has, to our knowledge, not been tested. We present an exploratory evaluation of such a dichotomy using a mixture distribution algorithm. METHODS: We analyzed the migration (as determined by RSA) of 147 cemented acetabular cups of 7 different designs by using a new set of algorithms for frequency distribution analysis called Rmix. RESULTS: We first analyzed a migration vector, regardless of direction. After 2 years there was a significant dichotomy between 2 lognormal subgroups within the sample. Although some types of cups were over-represented in one of the subgroups, neither cup design, sex, nor operating department could explain the dichotomy into two groups, which appears to reflect the existence of two basically different types of behavior of the cups. We next analyzed the migration along the 3 axes in space, and found a similar dichotomy. During the second year, around 80% of the patients belonged to a distinct, normally distributed subgroup with a mean not different from 0 mm and a small variation. The remainder differed significantly from this subgroup and showed migration. INTERPRETATION: There is a dichotomy in migration pattern. During the second postoperative year, most cups belonged to a subpopulation that appeared stable. The remainder is probably at risk of loosening. For a single type of prosthesis, the relative size of the stable subgroup may be a good index of the expected performance. The possibility of detecting subgroups within a seemingly continuous sample might be useful in many fields of medicine.
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13. |
- Aspenberg, Per, et al.
(författare)
-
Kustfåglar i Gävleborg 2007
- 2009
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Det främsta syftet med inventeringen 2007 var att kartlägga förekomsten av häckandekustfåglar detta år, för att genom jämförelse med motsvarande siffror från tidigareinventeringar få en uppfattning om populationsutvecklingen. Andra syften var att samla indata om onormal fågeldöd och om olika aspekter på skötsel av skyddade områden, t ex statusför skyltning. De kustfåglar som inventerats är främst fågelarter som är knutna till vattenmiljön, dvssjöfåglar, måsar, tärnor och vadare. Därutöver inkluderades andra arter utanför dessakategorier som har sin regionala utbredning begränsad till just skärgårdsmiljö (t exskärpiplärka) samt gråhäger och ängspiplärka som är relativt lättinventerade arter med enfaunistiskt intressant förekomst i skärgården. För storskarv och häger skedde (liksom 1997) en systematisk boräkning. I övrigt användesantalet närvarande fåglar som underlag för uppskattningar av antalet häckande par. För att tillfredsställa möjligheterna till goda jämförelser tio år bakåt i tiden användes nu,liksom 1997, en metodik innebärande tre räkningstillfällen. Den första räkningen var inriktadpå sjöfåglar (men noteringar gjordes för alla observerade fåglar) och genomfördestidsperioden 28 april – 13 maj. Den andra räkningen genomfördes i huvudsak 31 maj – 16juni. Vid båda dessa taxeringsomgångar genomkorsades länets skärgård av de två författarnatillsammans i en öppen båt från länsgränsen mot Uppland i söder till gränsen mot Medelpad inorr. Den tredje taxeringsomgången genomfördes under perioden 18 juni – 22 juli. Vid dennaomgång, som huvudsakligen syftade till att studera reproduktion, minkpredation och onormalsjöfågeldöd, arbetade författarna parallellt på olika håll. En jämförelse av resultatet för 2007 med tidigare inventeringar visar exempel på arter med enuppseendeväckande populationsökning såväl som arter med en lika kraftig minskning inomlänets gränser. Populationsökningarna kan bero på en ökad födotillgång till följd av eutrofiering. Även enförbättrad miljögiftssituation och minskad jakt kan spela in. Minskningar av populationerberor sannolikt på predation från framför allt mink. Resultatet kan sammanfattas i nedanstående tabell, där förändringar mellan 1997 och 2007samt möjliga orsaker till dessa redovisas för olika artgrupper. ArtgruppTrendMöjlig orsakDoppingarStark ökningEutrofieringStorskarvExplosionsartad ökningMinskad jakt, ökad födotillgång Svanar & gässÖkningMinskad jaktSimänderÖkningEutrofiering DykänderSplittrad bildOlika påverkan av minkVadareMinskning (dock ej f.strandskataEutrofiering? Mink? Flyttning – övervintring?LabbViss ökningFler tärnorSkrattmåsÖkningOmflyttning från insjöar till skärgård,eutrofieringÖvriga måsfåglarTämligen oförändrat Fisk- och silvertärnaÖkningÖkad födotillgångAlkfåglarÖkad födotillgångPredation från mink och ökad födotillgång Återgivning av tabell 2 från avsnitt 6.1.2 i rapporten. Ett intryck som förstärktes under fältarbetet våren-sommaren 2007 var skillnaden mellanfågelrika och fågelfattiga skärgårdsavsnitt. I stort sett tycks samma geografiska skillnader somnoterades under inventeringen 1997-1998 kvarstå.Resultaten visar att onormal sjöfågeldöd betingat av sjukdom och/eller toxiner endastförekom i mycket ringa omfattning denna sommar. Betydande ungförluster förorsakade avmink kunde dock dokumenteras för de markhäckande kustfåglarna och det kan konstateras attproblemet kvarstår i tämligen oförminskad omfattning. Förslag på åtgärder för att minska hoten mot kustfåglarna inkluderar fortsatt övervakning avskärgårdens toppkonsumenter och miljögifter, skapa säkrare farleder och navigationssystemför att minska risken för oljeolyckor, fortsatt uppföljning av trutsjukan samt stimuleradecimeringen av mink. Även hänsyn vid planering och exploatering längs kusten ansesangeläget, liksom aktiva åtgärder för att minska igenväxningen av öppna strandängar ochvissa fågelskär utan högre vegetation. Slutligen bör häckfågellivet i skärgårdarna undersökasäven framöver med tanke på den förväntade klimatförändringen.
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14. |
- Aspenberg, Per, et al.
(författare)
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Metodjämförelse av undersökningstyper för kustfåglar
- 2009
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Sommaren 2008 genomfördes jämförande studier mellan två olika inventeringsmetoder förkustfågeltaxering. Fältarbetet skedde efter en elva kilometer lång skärgårdssträcka i södraGävleborgs län. Syftet med studien var att studera skillnaden i utfall med att taxera kustfåglargenom dels den s.k. Anderssons metod och dels en senare av länsstyrelsen i Gävleborgbeskriven förenklad metod. Båda metoderna innehåller en tidig andfågelräkning som intebehandlades. Jämförelsen skedde bara mellan metodernas utfall i den senare inventeringsfasen,vilket för Anderssons metod innebar två inventeringstillfällen och för den nya metoden ett samlat inventeringstillfälle. De arter som var föremål för räkning i Anderssons första inventeringstillfälle fick sammantaget en högre numerär där än i den nya metoden med en enda integrerad räkning (ca 25 % högre). Hela skillnaden kunde förklaras av en stor diskrepans för småskrak. De arter som var föremål för räkning i Anderssons andra inventeringstillfälle fick omvänt en högre sammanlagd numerär i den nya metoden (också ca 25 % skillnad). Studien var upplagd med jämförande taxeringar med ganska stora tidsmellanrum. Det bedömssom att båda de ovan beskrivna skillnaderna huvudsakligen kunde förklaras av säsongsmässigaskillnader. Tidpunkten för inventeringen skulle alltså vara viktigare än vilken av detvå metoderna som väljs. Även behovet av landstigning undersöktes genom jämförelser mellan observationer från båtföre landstigning på ön och efter landstigning. De arter som då främst studerades varmåsfåglar, tärnor och vadare. För samtliga dessa grupper gav landstigning inte oväntat någothögre numerärer än räkningar från båt. För måsfåglar och tärnor sågs dock från närgången båtså mycket som 80-90% av antalet inräknade efter landstigning. För vadare indikeradeundersökningen ett lägre utfall från båt på runt 60%.
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15. |
- Aspenberg, Per, et al.
(författare)
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Metodstudie Kustfågelinventering 2007
- 2009
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Vid kustfågelinventering kan ingen inventerare se alla häckande fåglar vid ett enda besök.Den andel av de häckande fåglarna som en viss inventerare noterar vid ett visst tillfälle kankallas inventeringseffektivitet. Inventeringseffektiviteten skiljer sig mellan olika inventerareoch varierar under säsongen och mellan arter. Dessutom finns ett inslag av slumpmässigafaktorer som tillfällig frånvaro av fåglar, inventerarens ”dagsform”, väder m.m. Inventeringseffektiviteten undersöktes våren-sommaren 2007 genom en serie inventeringsbesök av sju olika observatörer vid tre fågelöar i Gävlebukten, huvudsakligen under perioden 23 maj – 2 juli. Sex av observatörerna saknade direkt erfarenhet av kustfågelinventering men hade alla mycket stora erfarenheter av fältornitologi och var därmed genomgående skickliga på artbestämning. Rent generellt kan man säga att ca 70 % var ett vanligt värde på inventeringseffektiviteten.För de mest lättinventerade arterna (t.ex. knölsvan, roskarl, rödbena) nåddes regelmässigt ca90 % inventeringseffektivitet, medan det för svårinventerade arter (t.ex. gräsand, drillsnäppa)snarare låg på 20-30 %. Inventeringseffektiviteten minskade under studieperioden, särskilt mot slutet. Dessutom vardet en påtaglig slumpmässig variation mellan olika inventeringsdagar under samma vecka,särskilt för kolonihäckande fåglar som kunde variera 10-20 procentenheter inom några dagar,för de tre öarna i testet. Man kan dock anta att denna korttidsvariation spelar mindre roll i enstörre inventering som sträcker sig över flera inventeringsdagar. Skillnaderna mellan de olika inventerarna var som regel 5-10 procentenheter. När det fannsrisk för sammanblandning av arter var dock skillnaden större, särskilt för blandade fisksilvertärnekolonier. Även för änderna som är generellt svårinventerade blev det storapersonskillnader. Skillnaderna var också mycket större för en ”ringrostig” inventerare somvarit mindre aktiv under några år. Personskillnaderna var delvis systematiska. Det berortroligen dels på ovana att räkna kolonihäckande fåglar (systematisk underskattning) samtskillnader i bedömning av fåglarnas uppträdande (häckar anden här eller är den bara tillfälliggäst vid ön). Dessa skillnader accentuerar värdet av att: använda samma inventerare helt eller delvis i manskapet mellan olika årintroducera nya inventerare i problematiken med att särskilja förväxlingsarterkoncentrera sig på ett urval av vissa arter vid ett inventeringsbesökanvända fotografering som dokumentationsmetod vid större vitfågelkolonierstyra upp fältanteckningarna med t ex strikt användning av protokollSlutsatser:Inventeringsresultat underskattar de verkliga populationsstorlekarnaDet är viktigt att inventerarna är tränade i just kustfågelinventering, och nyainventerare bör samkalibrera sig med mer erfarna.Även med tränad personal kommer ett visst fel att kvarstå, och småpopulationsförändringar (10-20 %) är mycket svåra att säkert skilja från metodfel. Försvårinventerade arter är metodfelet ofta avsevärt större.
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16. |
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17. |
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18. |
- Aspenberg, Per
(författare)
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Stimulation of tendon repair : Mechanical loading, GDFs and platelets. a mini-review
- 2007
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Ingår i: International Orthopaedics. - : Springer Science and Business Media LLC. - 0341-2695 .- 1432-5195. ; 31:6, s. 783-789
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Forskningsöversikt (refereegranskat)abstract
- The repair of subcutaneous tendon ruptures can be stimulated by a single application of one of several growth factors [e.g. platelet-derived growth factor (PDGF), transforming growth factor (TGF)-beta, insulin-like growth factor (IGF)-1, vascular endothelial growth factor (VEGF), bone morphogenetic proteins (BMPs) like growth differentiation factor (GDF)-5, -6, -7] or by a thrombocyte concentrate (PRP). The response to these measures is dependent on the mechanical microenvironment, which is crucial for repair. So far, almost all research has been limited to rodent models, mostly using the rat Achilles tendon. Ruptured human Achilles tendons appear to be mechanically loaded in spite of immobilisation. This suggests that the mechanical microenvironment might be favourable for the clinical use of growth factors or platelets for this indication. New methods to quantitate human Achilles tendon repair have been developed. © 2007 Springer-Verlag.
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19. |
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20. |
- Eliasson, Pernilla, et al.
(författare)
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Mechanical load and BMP signaling during tendon repair : A role for follistatin?
- 2008
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Ingår i: Clinical Orthopaedics and Related Research. - : Ovid Technologies (Wolters Kluwer Health). - 0009-921X .- 1528-1132. ; 466:7, s. 1592-1597
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Tidskriftsartikel (refereegranskat)abstract
- Healing of the rat Achilles tendon is sensitive to mechanical loading, and the callus strength is reduced by 3/4 after 14 days, if loading is prevented. Exogenous GDFs stimulate tendon healing. This response is influenced by loading: without loading, cartilage and bone formation is initiated. This implies BMP signaling is crucial during tendon healing and influenced by mechanical loading. We therefore asked if mechanical loading influences the gene expression of the BMP signaling system in intact and healing tendons, and how the BMP signaling system changes during healing. The genes were four BMPs (OP-1/BMP-7, GDF-5/CDMP-1/BMP-14, GDF-6/CDMP2/BMP-13, and GDF-7/CDMP-3/BMP-12), two receptors (BMPR1b and BMPR2), and the antagonists follistatin and noggin. The Achilles tendon was transected in rats and left to heal. Half of the rats had one Achilles tendon unloaded by injection of Botox in the calf muscles. Ten tendons were analyzed before transection and for each of four time points. All genes except noggin were expressed at all points, but followed different patterns during healing. Loading strongly decreased the expression of follistatin, which could lead to increased signaling. The BMP system appears involved in tendon maintenance and healing, and may respond to mechanical loading.
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21. |
- Eliasson, Pernilla, et al.
(författare)
-
Myostatin in tendon maintenance and repair
- 2009
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Ingår i: Growth Factors. - : Informa UK Limited. - 0897-7194 .- 1029-2292. ; 27:4, s. 247-254
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Tidskriftsartikel (refereegranskat)abstract
- Myostatin, a negative regulator of muscle growth, has recently been found to be expressed in tendons. Myostatin-deficient mice have weak and brittle tendons, which suggest that myostatin could be important for tendon maintenance. Follistatin expression in the callus tissue after tendon transection is influenced by loading. We found that follistatin antagonises myostatin, but not GDF-5 or OP-1 in vitro. To study if myostatin might play a physiological role in soft tissue, we transected 64 rat Achilles tendons and studied the gene expression for myostatin and its receptors at four different time-points during healing. Intact tendons were also studied. All samples were studied with or without mechanical loading. Unloading was achieved with botulinum toxin injections in the calf muscles. The expression of the myostatin gene was more than 40 times higher in intact tendons than in the callus tissue during tendon healing. The expression of myostatin was also influenced by loading status in both intact and healing tendons. Thereafter, we measured the mechanical properties of healing tendons after local myostatin administration. This treatment increased the volume and the contraction of the callus after 8 days, but did not improve its strength. Our results indicate that myostatin plays a positive role in tendon maintenance and that exogenous protein administration stimulates proliferation and growth of early repair tissue. However, no effect on further development towards connective tissue formation was found.
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22. |
- Eliasson, Pernilla, et al.
(författare)
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Rat Achilles tendon healing : mechanical loading and gene expression
- 2009
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Ingår i: JOURNAL OF APPLIED PHYSIOLOGY. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 107:2, s. 399-407
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Tidskriftsartikel (refereegranskat)abstract
- Injured tendons require mechanical tension for optimal healing, but it is unclear which genes are upregulated and responsible for this effect. We unloaded one Achilles tendon in rats by Botox injections in the calf muscles. The tendon was then transected and left to heal. We studied mechanical properties of the tendon calluses, as well as mRNA expression, and compared them with loaded controls. Tendon calluses were studied 3, 8, 14, and 21 days after transection. Intact tendons were studied similarly for comparison. Altogether 110 rats were used. The genes were chosen for proteins marking inflammation, growth, extracellular matrix, and tendon specificity. In intact tendons, procollagen III and tenascin-C were more expressed in loaded than unloaded tendons, but none of the other genes was affected. In healing tendons, loading status had small effects on the selected genes. However, TNF-alpha transforming growth factor-beta 1, and procollagens I and III were less expressed in loaded callus tissue at day 3. At day 8 procollagens I and III, lysyl oxidase, and scleraxis had a lower expression in loaded calluses. However, by days 14 and 21, procollagen I, cartilage oligomeric matrix protein, tenascin-C, tenomodulin, and scleraxis were all more expressed in loaded calluses. In healing tendons, the transverse area was larger in loaded samples, but material properties were unaffected, or even impaired. Thus mechanical loading is important for growth of the callus but not its mechanical quality. The main effect of loading during healing might thereby be sought among growth stimulators. In the late phase of healing, tendon-specific genes (scleraxis and tenomodulin) were upregulated with loading, and the healing tissue might to some extent represent a regenerate rather than a scar.
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23. |
- Eliasson, Pernilla, et al.
(författare)
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Unloaded rat Achilles tendons continue to grow, but lose viscoelasticity
- 2007
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Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 103:2, s. 459-463
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Tidskriftsartikel (refereegranskat)abstract
- Tendons can function as springs and thereby preserve energy during cyclic loading. They might also have damping properties, which, hypothetically, could reduce risk of microinjuries due to fatigue at sites of local stress concentration within the tendon. At mechanical testing, damping will appear as hysteresis. How is damping influenced by training or disuse? Does training decrease hysteresis, thereby making the tendon a better spring, or increase hysteresis and thus improve damping? Seventy-eight female 10-wk-old Sprague-Dawley rats were randomized to three groups. Two groups had botulinum toxin injected into the calf muscles to unload the left Achilles tendon through muscle paralysis. One of these groups was given doxycycline, as a systemic matrix metalloproteinase inhibitor. The third group served as loaded controls. The Achilles tendons were harvested after 1 or 6 wk for biomechanical testing. An increase with time was seen in tendon dry weight, wet weight, water content, transverse area, length, stiffness, force at failure, and energy uptake in all three groups (P < 0.001 for each parameter). Disuse had no effect on these parameters. Creep was decreased with time in all groups. The only significant effect of disuse was on hysteresis (P = 0.004) and creep (P = 0.007), which both decreased with disuse compared with control, and on modulus, which was increased (P = 0.008). Normalized glycosaminoglycan content was unaffected by time and disuse. No effect of doxycycline was observed. The results suggest that in growing animals, the tendons continue to grow regardless of mechanical loading history, whereas maintenance of damping properties requires mechanical stimulation.
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24. |
- Fahlgren, Anna, 1972-, et al.
(författare)
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A capsular incision leads to a fast osteoarthritic response, but also elevated levels of activated osteogenic protein-1 in rabbit knee joint cartilage
- 2006
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : Wiley. - 0905-7188 .- 1600-0838. ; 16:6, s. 456-462
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Tidskriftsartikel (refereegranskat)abstract
- We studied whether a small capsular incision alone, or combined with meniscectomy could induce early osteoarthritic changes in the rabbit knee. Thirty-one rabbits were operated on with a capsular incision in the left knee and meniscectomy in the right knee. Another 12 rabbits were used as controls. The rabbits were killed 3, 6 and 12 weeks after surgery. Osteoarthritic changes in the articular cartilage were evaluated by the modified Mankin score. The subchondral bone was evaluated by scintimetry (99mTc-HDP) and semiquantitative grading of histological changes. Osteogenic protein (OP-1) in its mature and pro-form was examined by immunohistochemistry. Both a capsular incision and meniscectomy induced articular cartilage fibrillation and increased bone metabolic activity during the initial weeks after surgery. Capsular incision led to lesser changes than meniscectomy. Mature OP-1 was elevated, and its pro-form reduced, in meniscectomized knees. A similar pattern was observed in knees with capsular incision. Already 3 weeks after surgery, the articular cartilage and subchondral bone showed typical signs of early osteoarthritis (OA), and a reparative response was suggested by increased intensity of OP-1 staining. As these signs were also found in knees with capsular incision only, it appears that trauma-related factors such as increased bleeding and inflammation are critical for the development of OA. Copyright © Blackwell Munksgaard 2006.
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25. |
- Goldhahn, Jörg, et al.
(författare)
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Clinical evaluation of medicinal products for acceleration of fracture healing in patients with osteoporosis
- 2008
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 43:2, s. 343-347
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Tidskriftsartikel (refereegranskat)abstract
- Pre-clinical studies indicate that pharmacologic agents can augment fracture union. If these pharmacologic approaches could be translated into clinical benefit and offered to patients with osteoporosis or patients with other risks for impaired fracture union (e.g. in subjects with large defects or open fractures with high complication rate), they could provide an important adjunct to the treatment of fractures. However, widely accepted guidelines are important to encourage the conduct of studies to evaluate bioactive substances, drugs, and new agents that may promote fracture union and subsequent return to normal function. A consensus process was initiated to provide recommendations for the clinical evaluation of potential therapies to augment fracture repair in patients with meta- and diaphyseal fractures. Based on the characteristics of fracture healing and fixation, the following study objectives of a clinical study may be appropriate: a) acceleration of fracture union, b) acceleration of return to normal function and c) reduction of fracture healing complications. The intended goal(s) should determine subsequent study methodology. While an acceleration of return to normal function or a reduction of fracture healing complications in and of themselves may be sufficient primary study endpoints for a phase 3 pivotal study, acceleration of fracture union alone is not. Radiographic evaluation may either occur at multiple time points during the healing process with the aim of measuring the time taken to reach a defined status (e.g. cortical bridging of three cortices or disappearance of fracture lines), or could be obtained at a single pre-determined timepoint, were patients are expected to reach a common clinical milestone (i.e. pain free full weight-bearing in weight-bearing fracture cases). Validated Patient Reported Outcomes (PRO's) measures will need to support the return to normal function co-primary endpoints. If reduction of complication rate (e.g. non-union) is the primary objective, the anticipated complications must be defined in the study protocol, along with their possible associations with the specified fracture type and fixation device. The study design should be randomized, parallel, double-blind, and placebo-controlled, and all fracture subjects should receive a standardized method of fracture fixation, defined as Standard of Care. © 2008 Elsevier Inc. All rights reserved.
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