Biomedical subjects

Nils Hansen-Algenstaedt

Publications and source records attributed to Nils Hansen-Algenstaedt.

5 recordsLinked to original sources

PubMed2006

Sequential changes in vessel formation and micro-vascular function during bone repair.

BACKGROUND: Angiogenesis, the process of new vessel formation from a pre-existing vascular network, is essential for bone development and repair. New vessel formation and microvascular functions are crucial during bone repair, not only for sufficient nutrient supply, transport of macromolecules and invading cells, but also because they govern the metabolic microenvironment. Despite its central role, very little is known about the initial processes of vessel formation and microvascular function during bone repair. METHODS: To visualize and quantify the process of vessel formation and microvascular function during bone repair, we transplanted neonatal femora with a substantial defect into dorsal skin-fold chambers in severe combined immunodeficient (SCID) mice for continuous noninvasive in-vivo evaluation. We employed intravital microscopic techniques to monitor effective microvascular permeability, functional vascular density, blood flow rate and leukocyte flux repeatedly over 16 days. Oxytetracyclin and v. Kossa/v. Giesson staining was performed to quantify the calcification process in vivo and in vitro. RESULTS: Development of a hematoma surrounding the defect area was the initial event, which was accompanied by a significant increase in microvascular permeability and blood flow rate. With absorption of the hematoma and vessel maturation, permeability decreased continuously, while vascular density and tissue perfusion increased. Histological evaluation revealed that the remodeling of the substantial defect prolonged the in-vivo monitored calcification process. INTERPRETATION: The size of the initial substantial defect correlated positively with increased permeability, suggesting improved release of permeability-inducing cytokines. The unchanged permeability in the control group with boiled bones and a substantial defect corroborated these findings. The adaptation to increasing metabolic demands was initially mediated by increased blood flow rate, later with increasing vascular density through increased tissue perfusion rate. These insights into the sequence of microvascular alterations may assist in the development of targeted drug delivery therapies and caution against the use of permeability-altering drugs during bone healing.

Animals↗

PubMed2005

Long-term observation reveals time-course-dependent characteristics of tumour vascularisation.

Functional properties of tumour vasculature influence the process of metastasis and play a role in generating a heterogeneous metabolic microenvironment, which contributes to genetic instability and inefficiency of tumour therapies. Morphological and functional properties of tumour vasculature may vary from tumour onset to late-stage disease. The aim of this study was to identify the dynamic alteration in tumour microcirculation in a chronic observation model. Invasively-growing, non-disseminating, green fluorescent protein transfected, human bone marrow derived endothelial cells, were implanted into cranial windows of severe combined immunodeficient mice. Intravital fluorescence microscopy was performed over a period of 85 days to measure permeability, leucocyte-endothelial interaction (LEI) and tissue perfusion rate as functional parameters. Vessel density, branching pattern and scanning electron microscopy were monitored as morphological parameters. Concordant with an increasing count of transendothelial pores, the results show that the initial event following tumour cell implantation was a significant increase in the permeability of pre-existing vessels. The variations in newly formed vessels were characterised by sequentially-occurring functional and morphological alterations with the development of characteristics typical of tumour vessels, such as increased count of trifurcations and variation in vessel calibre by more than 100%. In parallel with the increasing vessel volume per area, the tissue perfusion rate increased until day 61. It is concluded from the step-specific sequential functional and morphological alterations that the efficiency of adjuvant therapies depends not only on their intrinsic efficiency but also on the timing of their initiation.

Animals↗

PubMed2003

High migration rate of two types of threaded acetabular cups.

INTRODUCTION: Survivorship analysis was performed on 479 Link V-type threaded cups and on 110 modified V-type Bad Bramstedt cups (a modification of the Link V-type cup since 1993 with a smaller primary coil) to evaluate the effect of the modifications. MATERIALS AND METHODS: Indication for hip arthroplasty with a Link V-type cup was an inflammatory arthritis in 310 patients, osteoarthritis in 138 patients and dysplastic hip joints in 31 patients. The average follow-up was 8.6+/-3.2 (range 3.0-15.2) years. The 110 modified V-type Bad Bramstedt cups had a mean follow-up period of 4.5+/-0.7 (range 3.0-5.9) years, including 49 with inflammatory arthritis, 49 with osteoarthritis and 12 with dysplastic hip joints. To evaluate the migration rate and radiolucent lines, radiographical examination according to the method of Nunn et al. and Delee and Charnley was performed on 264 Link V-type cups with a mean follow-up period of 8.2+/-2.7 years and 59 modified V-type Bad Bramstedt cups with a mean follow-up period of 4.6+/-0.7 years. Relevant parameters influencing cup migration were analysed. RESULTS: The cumulative survival rate of the former Link V-type acetabular cup was 94.5% after 5 years, 88.1% after 10 years and 70.2% after 15 years. The Bad Bramstedt cup showed a 5-year survivorship rate of 97.9%. Migration of more than 3 mm or tilting of the cup greater than 5 degrees was found in 73% of the former type and in 39% of the modified cup. Radiolucent lines greater than 2 mm and detectable in two zones appeared in 6.4% of the former Link V-type and in 1.7% of the Bad Bramstedt cup design. Among the influencing factors analysed, length of follow-up and primary cup positioning showed a significant correlation to cup migration. CONCLUSION: The modification of the Link V-type cup showed no satisfactory improvement in cup migration. Therefore, both threaded cups were abandoned in favour of cementless press-fit cups.

Acetabulum↗

PubMed2003

Bilaterally increased VEGF-levels in muscles during experimental unilateral callus distraction.

Angiogenesis is essential for wound healing and proliferative processes such as bone formation and repair. Since increased expression of the vascular endothelial growth factor (VEGF) stimulates bone formation, it can be hypothesized that surgical procedures leading to a systemic increase of VEGF for instance during wound healing, influence enchondral ossification processes and might be responsible for observed growth phenomena during callus distraction. To study the mechanisms of angiogenesis in soft tissue during unilateral callus distraction, lengthening of the right tibia was performed in 12 beagles. After osteotomy, application of a ring fixator and after five latency days, distraction was started for 25 days. A control group of four additional beagles underwent no surgical procedure. Subsequent to the distraction period (Group A), muscle samples from six beagles were taken from the distracted side (ds) and the contralateral non-distracted side (n-ds), six beagles underwent an additional consolidation period of 25 days (Group B). Samples were analyzed for VEGF, VEGFR-1 and VEGFR-2 mRNA expression using real-time PCR and protein expression using Western Blot analysis. Muscles from both extremities showed significantly increased expression of VEGF and its cognate receptors VEGFR-1/2. Expression decreased significantly after the consolidation period, whereby the level at the non-distracted side decreased more than the level at the distracted side. Interestingly VEGF and VEGFR-1 levels at the non-distracted side were significantly higher than at the distracted side. In contrast VEGFR-2, the receptor that mediates endothelial cell proliferation, showed higher levels at the distracted than at the non-distracted side. These findings indicate that callus distraction results not only in locally increased expression of VEGF and its receptors, but leads also to increased VEGF and VEGFR-1/2 levels at distant sides and might therefore be responsible for the observed growth phenomena during callus distraction.

Animals↗

PubMed2003

Microvascular alterations in diabetic mice correlate with level of hyperglycemia.

Vascular alterations are the most common causes of morbidity and mortality in diabetic patients. Despite the impact of endothelial dysfunction on microcirculatory properties, little is known about the endothelial cell alteration during the development of diabetes and its correlation to the metabolic situation. For that reason we continuously monitored in vivo functional and morphological alterations of the microvasculature in hyperglycemic and hyperinsulinemic transgenic UCP1/DTA mice with brown fat deficiency, using a dorsal skin-fold chamber preparation and fluorescence microscopy. UCP1/DTA mice showed a dramatic decrease in vascular density due to a remarkable reduction of small vessels. Vascular permeability and leukocyte endothelial interactions (LEIs) significantly increased. The extent of vascular alteration correlated with the extent of metabolic dysfunction. Decreased tissue perfusion observed in UCP1/DTA mice might play a role in impaired wound healing observed in diabetes. The increased permeability in subcutaneous tissue may serve as predictor of vascular changes in early stages of diabetes. The increased LEI and serum tumor necrosis factor-alpha levels, which mirror the inflammatory process, support the growing evidence of the inflammatory component of diabetic disease. The results suggest that anti-inflammatory strategies might be able to prevent vascular deterioration in early stages of diabetes. Further investigations are required to evaluate the benefit of such therapeutic strategies.

Animals↗