Use of Imatinib in the Prevention of Heterotopic Ossification

Background

Heterotopic ossification (HO) is a common complication following orthopedic and trauma surgery, which may have substantial negative effects on the postoperative outcome. Angiogenesis appears to play a critical role in heterotopic ossification. One of the involved signaling molecules is platelet-derived growth factor (PDGF) which may be inhibited by imatinib.

Questions/Purposes

Our goal was to prevent HO by pharmacologically interfering with the molecular signaling pathways involved in the developmental process. We hypothesized that by administering a proven inhibitor of PDGF expression, heterotopic bone formation may be prevented.

Methods

The effect of imatinib on HO formation was studied in a murine model which reliably produces islets of HO within the soft tissue following Achilles tenotomy. The control group underwent Achilles tenotomy only. The imatinib group received imatinib mesylate. After trial completion, the limbs were harvested and scanned by micro-CT. Heterotopic bone volume was then identified and quantified.

Results

The mean volume of heterotopic bone formed in the control group was 0.976mm³ compared to 0.221 mm³ in the imatinib group. The volume of HO in the treatment group was reduced by 85% compared to the control group.

Conclusions

The administration of imatinib was associated with a significantly reduced volume of HO. This may be due to the inhibitory effect of imatinib on the PDGF signaling pathway during development of HO.

Clinical Relevance

The successful reduction of HO formation following imatinib administration has led to further insight concerning the pathogenesis of HO which in the future may lead to new clinical approaches towards the prevention of HO.

Electronic supplementary material

The online version of this article (doi:10.1007/s11420-013-9335-y) contains supplementary material, which is available to authorized users.     

Wie häufig werden Patienten mit depressiven Störungen in der hausärztlichen Praxis erkannt?

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Hausärzte sind als Primärversorger für Patienten mit depressiven Störungen entscheidende Weichensteller...     

Case reports

The clinical presentation of lead intoxication may vary widely and in the absence of a high clinical index of suspicion, the diagnosis may be missed. The effects of lead on mitochondrial oxidative phosphorylation and its interaction with calcium-mediated processes explain the heterogenous presentation. In this case report, the diagnosis was finally made when bilateral wrist drop developed on top of abdominal cramps and anemia. Before, ascites raised the suspicion of a tumor. Therefore, each element of the triad of unexplained anemia, abdominal cramps, and bilateral wrist (or foot) drop should lead any physician to consider the diagnosis of lead intoxication. This case also illustrates the importance of a careful and meticulous social history in patient management.     

CD74 indicates microglial activation in experimental diabetic retinopathy and exogenous methylglyoxal mimics the response in normoglycemic retina

Diabetes induces vasoregression, neurodegeneration and glial activation in the retina. Formation of advanced glycation endoproducts (AGEs) is increased in diabetes and contributes to the pathogenesis of diabetic retinopathy. CD74 is increased in activated microglia in a rat model developing both neurodegeneration and vasoregression. In this study, we aimed at investigating whether glucose and major AGE precursor methylglyoxal induce increased CD74 expression in the retina. Expression of CD74 in retinal microglia was analyzed in streptozotocin-diabetic rats by wholemount immunofluorescence. Nondiabetic mice were intravitreally injected with methylglyoxal. Expression of CD74 was studied by retinal wholemount immunofluorescence and quantitative real-time PCR, 48 h after the injection. CD74-positive cells were increased in diabetic 4-month retinas. These cells represented a subpopulation of CD11b-labeled activated microglia and were mainly located in the superficial vascular layer (13.7-fold increase compared to nondiabetic group). Methylglyoxal induced an 9.4-fold increase of CD74-positive cells in the superficial vascular layer and elevated gene expression of CD74 in the mouse retina 2.8-fold. In summary, we identified CD74 as a microglial activation marker in the diabetic retina. Exogenous methylglyoxal mimics the response in normoglycemic retina. This suggests that methylglyoxal is important in mediating microglial activation in the diabetic retina.     

Reactive groups on polymer covered electrodes, 4. Lactate-oxidase-biosensor based on electrodes modified by polythiophene

Electrocopolymerization of 3-thiopheneacetic acid ( 1 ) and 3-methylthiophene ( 2 ) under various conditions produces poly{(3-methylthiophene-2,5-diyl)-co-[3-(carboxymethyl)thiophene-2,5-diyl]} ( 3 ). By activation of the carboxy groups with dicyclohexylcarbodiimide (DCC) lactate oxidase (LOD) is covalently bonded to the surface of the electrode. In this way a lactate sensor was formed which is applicable for the determination of lactate in micromolar concentrations.