Kollagen Typ I, als wesentlicher Bestandteil der ECM, spielt eine entscheidende Rolle in der Wundheilung nach Myokardinfarkt. Zum einen ist eine ausreichende Narbenbildung zur Gewährleistung der Ventrikelstabilität notwendig, zum anderen führt eine überschießende Kollagensynthese mit interstitieller Fibrose des Myokards zu einer kontraktilen Dysfunktion des Ventrikels. Inwiefern sich eine Verminderung oder das Fehlen an Kollagen Typ I auf die Wundheilung und das Remodeling auswirkt, untersuchten wir am Modell der Osteogenesis Imperfecta Maus (OIM). 12-16 Wochen alte homozygote OIM Tiere, sowie heterozygote und homozygote Kontrollen, wurden einer Unterbindung der linken Koronararterie mit konsekutiven Myokardinfarkt (AMI) oder einer „Schein“- Infarzierung unterzogen. Echokardiographische Kontrollen der Ventrikelfunktion erfolgten am Tag vor, am Tag 1, Tag 8 und 8 Wochen nach AMI und „Schein“- Infarzierung, bevor wir die Tiere opferten. Das experimentelle Protokoll ex vivo zur Analyse der mechanischen Eigenschaften des Gewebes und des Kontraktionsverhaltens umfasste die Bestimmung der isometrischen Kraft und der Kraft- Frequenz- Beziehung. Außerdem wurden alle Herzen unabhängig vom Zeitpunkt des Todes histologisch aufgearbeitet 1. zur Infarktgrößenbestimmung, 2. zur immunhistologischen Bestimmung des Kollagengehalts und 3. zur Untersuchung der Todesursache bei vorzeitigem Tod. Vor Beginn der Studie fanden wir keine Unterschiede zwischen den OIM-/- und den Kontrollgruppen in ihrer Ventrikelfunktion. In der frühen Phase (Tag 3 bis 7) nach AMI war die Sterblichkeitsrate der OIM-/- aufgrund von Ventrikelrupturen signifikant erhöht verglichen mit den Kontrollen (54% OIM-/- vs. 13% WT). Wir konnten keine Abhängigkeit von der Infarktgrösse als ursächlichen Faktor auf das Entstehen einer Ruptur beobachten, da auch Tiere ohne makro- und mikroskopischen Nachweis eines Infarktes aus diesem Grund verstarben. Nach 8 Wochen präsentierten die OIM-/- eine signifikant niedrigere Dilatation des linken Ventrikels, sowie einen geringeren linksventrikulären Durchmesser verglichen mit den Kontrollgruppen. In den muskelphysiologischen Versuchen der isometrischen Kraftentwicklung konnte sowohl in der Infarkt- als auch in der Sham- Gruppe eine höhere maximale Kraft der OIM-/- verglichen mit den heterozygoten und homozygoten Kontrollen beobachtet werden. Zum Erreichen vergleichbarer Kraftniveaus war bei den homozygoten OIM eine signifikant grössere Vordehnung notwendig, was indirekt für eine höhere Gewebecompliance spricht. Der Kollagengehalt in der Infarktnarbe der OIM-/- war gegenüber den OIM+/- und WT Tieren signifkant erniedrigt. Keine Unterschiede in den drei Gruppen fanden sich in der Infarktgrössenentwicklung nach AMI. / Background: Collagen synthesis is an important process in early wound healing after myocardial infarction (MI). Interstitial fibrosis during chronic post infarction remodelling however is associated with impaired ventricular function. To assess the role of collagen I after MI we studied a mouse model of osteogenesis imperfecta (OI). Homozygous OI mice (OIM) lack pro-alpha 2 -(I) collagen, a defect that was previously shown to be associated with decreased chamber stiffness but normal left ventricular dimensions and systolic function. Methods: 12-16 weeks old homozygous, heterozygous OIM mice and wild type mice were subjected to a chronic myocardial infarction protocol or sham operation. Echocardiographic studies were performed before operation, on day 1, 8 and before sacrifice after 8 weeks. In a second group all animals were sacrificed on day 2. Collagen was quantified histologicaly and by real-time PCR. Matrixmetalloproteinase-9 (MMP-9) expression in infarct border zone 2 days after MI was assessed by ELISA. Results: As determined by echocardiography baseline functional and geometrical parameters were not different between genotypes. After MI but not after sham operation homozygous OIM mice showed a significantly increased mortality due to early ventricular rupture (54% oim/oim vs 13% wt/wt) between day 3 and 7. Occurrence of fatal rupture was independent of infarct size. Surviving OIM mice revealed significantly less ventricular dilation when compared with heterozygous after completing the 8 weeks period. Infarct size was not different between genotypes after 2 days or 8 weeks. OIM mice revealed increased ventricular diameter as determined by echocardiography on day 1. Homozygous OIM showed significantly less collagen I mRNA within the infarct area. MMP-9 expression in the infarct border zone was significantly higher in OIM animals 2 days after MI. Conclusion: In the present model of OI we observed a high mortality due to ventricular rupture after MI. Early ventricular dilation, less collagen I expression and increased MMP-9 activity within infarct area account for this fatal outcome after acute MI. The OIM mouse model demonstrates the importance collagen I for early myocardial wound healing as well as remodelling.

No description available.

Osteogenisis imperfecta (OI), eller medfödd benskörhet, är en sällsynt bindvävssjukdom som gör skelettet skört. Barn med OI kan påverkas av återkommande frakturer, smärta, kotkompressioner och flertalet sjukhusvistelser. Det finns tidigare studier som beskriver barn med OI och deras föräldrars upplevelser av sjukdomen och dess vård, samtidigt saknas studier som belyser barnsjuksköterskans perspektiv. Syftet med denna studie var att beskriva barnsjuksköterskors erfarenheter av att vårda barn som har osteogenesis imperfecta. En kvalitativ design med induktiv ansats samt ett strategiskt urval tillämpades. Semistrukturerade intervjuer genomfördes med 14 barnsjuksköterskor från åtta svenska sjukhus. En induktiv innehållsanalys användes för att analysera insamlad data. I resultatet framkom tre kategorier: en utmanande omvårdnadssituation, betydelsen av personcentrerad vård och betydelsen av att arbeta i team med sju underkategorier; att vara på okänd mark, att anpassa omvårdnaden till benskörheten, att stötta och vägleda föräldrarna, att samarbeta med barn och föräldrar, att skapa kontinuitet, att samarbeta med kollegor och att ha tillgång till specialistteam. Det kan vara en utmaning att vårda barn med OI. Tillgång till specialistteam är viktigt och skapar trygghet för barnsjuksköterskor och familj. Stora geografiska avstånd och olika journalsystem komplicerar kommunikationen och informationsutbytet. Det finns en önskan om fler information- och kunskapskanaler såsom nyhetsbrev, föreläsningar online och sjuksköterskemöten.

Indiana University-Purdue University Indianapolis (IUPUI) / Current interventions used to reduce skeletal fragility are insufficient at enhancing bone across multiple hierarchical levels. Bisphosphonates, such as Zoledronate (ZOL), treat a variety of bone disorders by increasing bone mass and bone mineral density to decrease fracture risk. Despite the mass-based improvements, bisphosphonate use has been shown to compromise bone quality. Alternatively, Raloxifene (RAL) has recently been demonstrated to improve tissue quality and overall mechanical properties by binding to collagen and increasing tissue hydration in a cell-independent manner. We hypothesized that a combination of RAL and ZOL would improve mechanical and material properties of bone more than either monotherapy alone by enhancing both quantity and quality of bone. In this study, wildtype (WT) and heterozygous (OIM+/-) male mice from the Osteogenesis Imperfecta (OI) murine model were treated with either RAL, ZOL, or RAL and ZOL from 8 weeks to 16 weeks of age. Combination treatment resulted in higher trabecular architecture, cortical mechanical properties, and cortical fracture toughness in diseased mouse bone. Two fracture toughness properties, direct measures of the tissue’s ability to resist the initiation and propagation of a crack, were significantly improved with combination treatment in OIM+/- compared to control. There was no significant effect on fracture toughness with either monotherapy alone in either genotype. Following the mass-based effects of ZOL, bone volume fraction was significantly higher with combination treatment in both genotypes. Similar results were seen in trabecular number. Combination treatment resulted in higher ultimate stress in both genotypes, with RAL additionally increasing ultimate stress in OIM+/-. RAL and combination treatment in OIM+/- also produced a higher resilience compared to the control. Given no significant changes in cortical geometry, these mechanical alterations were likely driven by the quality-based effects of RAL. In conclusion, this study demonstrates the beneficial effects of using combination therapy to increase bone mass while simultaneously improving tissue quality, especially to enhance the mechanical integrity of diseased bone. Combination therapies could be a future mechanism to improve bone health and combat skeletal fragility on multiple hierarchical levels.

No description available.

No description available.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Missouri-Columbia, 2006. / Title from title screen of research.pdf file (viewed on December 22, 2006). The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. "May 2006" Vita. Includes bibliographical references.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 5 uppsatser.

A Osteogênese Imperfeita (OI) é caracterizada por fragilidade óssea e susceptibilidade a fraturas. As complicações da patologia podem afetar o desenvolvimento físico e motor, comprometendo as habilidades funcionais, o nível da marcha e a independência do indivíduo. Objetivo: Avaliar as características clínico-funcionais de crianças e adolescentes com Osteogênese Imperfeita (OI). Métodos: Estudo transversal no qual foram avaliados sujeitos de ambos os gêneros com idade entre 0 e 18 anos e diagnóstico de OI, em tratamento no CROI-RS. Os dados clínicos e funcionais foram coletados através de fichas específicas e avaliação funcional. Foram avaliados aspectos relacionados à presença de fraturas e deformidades ósseas, habilidade da marcha, força muscular e amplitude de movimento articular. A densidade mineral óssea (DMO) foi mensurada através do Dual Energy X-Ray Absoptometry (DEXA). O nível de significância adotado foi de 5% (p≤0,05). Resultados: Encontramos diferença significativa na ocorrência de fraturas, presença de deformidades ósseas, uso de haste intramedular, baixa densidade mineral óssea, tratamento medicamentoso e aspectos relacionados à marcha comparando OI tipo I, III e IV. As formas mais graves de OI (tipo III e IV) apresentaram fraturas nos primeiros meses de vida, maior deformidade óssea. Associação inversa entre amplitude de movimento articular geral e o nível da marcha e uma associação direta com idade de início de marcha, o número total de fraturas e a presença de deformidades ósseas. Encontrou-se uma associação direta entre a força muscular geral e o nível da marcha e uma associação inversa com a idade de início de marcha e presença de deformidades ósseas. Conclusão: Estes dados sugerem que as características clínico-funcionais variam de acordo com os tipos de OI. Nas formas moderada e grave de OI há maior limitação funcional influenciada pelo número de fraturas e presença de deformidades ósseas afetando negativamente o nível da marcha. / Osteogenesis Imperfecta (OI) is characterized by bone fragility and susceptibility to fractures. Complications of the disease can affect the physical and motor development, compromising the functional skills, level of gait and independence of the individual. Objective: To evaluate the clinical and functional features of children and adolescents with OI. Methods: A cross-sectional study which evaluated subjects of both genders aged between 0 and 18 years attended in the Reference Center for Treatment of OI of Rio Grande do Sul (CROI-RS). Clinical and functional data were evaluated through specific tokens and functional assessment. We evaluated aspects related to the presence of fractures and bone deformities, gait ability, muscle strength, joint range of motion and use of intramedullary rod. Bone mineral density (BMD) was measured by Dual Energy X-Ray Absoptometry (DEXA). The level of significance was set at 5% (p ≤ 0.05). Results: We found significant differences in the occurrence of fractures, presence of bone deformities, use of intramedullary rod, bone mineral density, drug therapy and aspects related to gait comparing OI types I, III and IV. The age of gait acquisition showed a direct association with overall joint range of motion and an inverse relationship with overall muscle strength. The level of ambulation was directly associated with overall muscle strength and inversely associated with overall joint range of motion. Conclusion: Our findings confirm that clinical and functional features vary according to OI type. Moderate and severe forms of OI are associated with greater functional limitation, influenced by fractures in early life, number of fractures and the presence of bone deformities, which negatively affect the acquisition and level of ambulation.